Cardiac Arrest

[Ace844]

Hello Everyone,

Here's a great teaching article on this subject...

Hope this helps,

ACE844

(End Points of Resuscitation

Mark D. Calkins @ MD*+

Christian Popa, MD+

Timothy B. Bentley, Ph.D.*

*Walter Reed Army Institute of Research

Department of Resuscitative Medicine

Silver Spring, MD 20910

+Walter Reed Army Medical Center

Departments of Critical Care and Anesthesiology

Washington, DC 20307 http://www.gasnet.org/esia/2000/november/ )

OBJECTIVES:

1. State necessity for full resuscitation of the shock patient.

2. Define shock.

3. Define oxygen debt.

4. State why end points of resuscitation literature should be approached with caution.

5. Define compensated shock.

6. Discuss end points of resuscitation typically used.

7. Define best end points of resuscitation based on the available data.

8. Become aware of potential future markers of successful resuscitation.

Introduction

Successful resuscitation of the trauma patient in the emergency department, the hemorrhaging patient in the operating room or the septic patient in the intensive care unit was once guided using only simple vital sign means. However, is a relatively normal blood pressure, heart rate and urine output enough? Initially that may be all we have, but should we resuscitate to other measures when we have the opportunity?

Should we worry about the other possible end points of resuscitation if our patient has a normal set of vital signs? If normal blood pressure, heart rate and urine output do not equal full resuscitation, does that matter? Several studies reveal the importance of fully resuscitating your patient. (1-5)

Inadequately resuscitating a patient in shock can lead to:

· Increased incidence of systemic inflammatory response syndrome (SIRS)

· Increased incidence of multi-organ dysfunction syndrome (MODS)

· Increased mortality

Fully resuscitating one’s patient out of shock implies knowing:

· that the patient is in shock and the reason why they went into shock

· the treatment you will use

· measures to assess attainment of your treatment goals.

We will define basic shock as:

· inadequacy of organ perfusion and tissue oxygenation.

Oxygen debt is defined as:

· a difference between oxygen consumption at baseline and oxygen consumption during shock.

There are several ways in which to categorize shock, which go beyond the scope of this paper. We will limit our discussion to the potential end points which may assist the clinician in providing full resuscitation.

One must be cautious when approaching the data regarding end points of resuscitation. Due to difficulties in studying severely ill patients, ideal studies are almost impossible to perform.

· Prospective, randomized, blinded resuscitation studies are rare.

· Many studies are observational looking at only outcomes, not using goal-directed therapies with intentions to treat randomized groups.

· In order to improve patient numbers, patient populations are often mixed, and it is not uncommon to see studies that include trauma patients, neurological patients, medical intensive care unit (MICU) patients and surgical intensive care unit (SICU) patients.

· Timing is a very important factor. Studies that include treatments that started later in a patient’s course run the risk of having less benefit for that patient.

Traditional Parameters

Most clinicians use blood pressure (BP), heart rate (HR) and urine output (UO) as a measure of the adequacy of perfusion. The literature has not extensively looked at these endpoints for patients in shock. Certainly, in the face of Advanced Trauma Life Support (ATLS)-defined Class IV hemorrhagic shock, these parameters are likely to be reliable indicators of inadequacy of perfusion. Unfortunately, many patients, including trauma patients not in Class IV hemorrhagic shock, are in a compensated shock.

· Compensated shock is defined as ongoing inadequate tissue perfusion in the presence of normal BP, HR and UO.

· This is potentially related to a maldistribution of blood flow. Eighty-five percent of 39 patients suffering from penetrating trauma had evidence of inadequate resuscitation despite normal HR, BP and UO. (6) Scalea et al. similarly looked at blunt trauma victims with head injuries. (7) They found that 80% percent of 40 patients had elevated blood lactates, despite normal vital signs and urine output.

· Few studies deal with simple vital signs and septic shock. Parker et al. showed that an initial heart rate of less than 106 beats per minute predicted survival in 48 septic shock patients. (8) Like many resuscitation end point articles, this one was simply observational, looking at data after grouping by outcome. Thus, tachycardia may be a marker for potentially lethal sepsis.

· Perhaps the most common situation where vitals signs are used as end points of resuscitation in the critical burn patient. Baxter et al. showed that crystalloid administered until BP and UO normalized led to improved survival in burn patients compared with historical controls. (9) Better survival in burn patients has been attributed to more aggressive fluid therapy. (10) However, resuscitation until fixed BP and UO goals are attained may not be adequate. Dries and Waxman, in a small retrospective study, found that 50% of patients had flow-dependent oxygen consumption (VO2), despite normal vital signs. (11) This was determined by administering fluid challenges to increase oxygen delivery (DO2) and noting if there was continued increase in VO2. Normal patients have VO2 that is not dependent upon DO2. Urine output and vital signs were not indicators of flow-dependent VO2 in these burn victims. Jeng et al. noted that average base deficit and blood lactate were abnormal despite normal vitals signs in burn patients resuscitated to normal vital signs and urine output. (12) Schiller et al. found better mortality rates when burn patients were resuscitated to hyperdynamic numbers than traditional end points. (13)

· It appears that conventional parameters may be inadequate as markers of sufficient resuscitation for patients in shock. Even in burn patients, further markers are probably desirable. Stopping resuscitation at normal blood pressure, heart rate and urine output may leave some patients in a state of compensated shock and therefore at risk for SIRS, MODS and death.

Cardiac Output

Few studies have addressed the use of cardiac output solely as an end point of resuscitation. One study found that multi-trauma patients who reached a left ventricular stroke work index (LVSWI) of 5,000,000 dyne-cm/ M2 or pulmonary artery occlusion pressure of > 10 mm Hg after fluid administration were more likely to survive. (14) It may be that ability to obtain a particular cardiac output is a marker for survival. The author concluded that CO is a proper criterion for adequate hemodynamic resuscitation of multi-trauma patients. Of interest, mean arterial blood pressure, heart rate, urine output and pulmonary artery occlusion pressure did not correlate with LVSWI. Schiller et al. found that survivors of burn injuries mount higher cardiac outputs. (15) Cardiac output appears to be a marker for survival in burns also.

In contrast to the above studies, Bakker et al., in an observational study of 48 patients, found no significant difference in cardiac index between survivors and nonsurvivors of septic shock. (16) In a multi-center, ICU study, Gattinoni et al. compared resuscitation to normal cardiac index with resuscitation to normal mixed venous saturation (SvO2) and resuscitation to supranormal oxygen delivery/consumption parameters. (17) They found no survival advantage for any one of these groups compared to the others.

Perhaps cardiac output is helpful as a marker of survival for patients suffering from hypovolemic shock, but not from septic shock. (18) Not much data looks at cardiac output specifically as an endpoint for resuscitation. Much of the literature uses the data with further cardiac indices.

Mixed Venous Oxygen Saturation (SvO2)

· Mixed venous oxygen saturation reflects the amount of oxygen remaining in blood after perfusing the tissues. Typically SvO2 falls if tissues is hypoperfused (due to increased extraction) and rises when tissue is hyperperfused. Logically, it would seem that an increase in SvO2 indicates no further need for oxygen at the cellular level. Unfortunately, this is not always true.

· In some states, such as septic shock, the tissues may not be able to extract the oxygen which passes. In this case, venous blood will return with a higher saturation level, not because the cells are adequately oxygenated, but because the cells could not remove the oxygen they needed.

· SvO2 is often used as an end point for cardiac surgery patients in the perioperative time period. In this instance however, the anesthesiologist, surgeon and intensivist are often using SvO2 as an indirect measure of cardiac output. Rearranging the Fick equation:

SvO2 = SaO2 – VO2 / [CO x Hgb]

where SaO2 represents the saturation of oxygen in the arterial blood, VO2 is oxygen consumption, CO is cardiac output and Hgb is hemoglobin. Assuming all other factors do not change, then changes in SvO2 correlate with changes in CO. Unfortunately, in shock states, ongoing changes in SaO2, VO2, CO and Hgb may make an SvO2-CO relationship difficult to interpret.

· In the Gattinoni study previously mentioned, using SvO2 as an end point of resuscitation for patients suffering from different types of shock, SvO2 produced similar results as resuscitation to a normal cardiac index or supranormal cardiac index. (17) Very little literature looks at SvO2 as an end point of resuscitation or compares it to metabolic indices that will be mentioned later in this review. Unfortunately, there is not enough data to support using SvO2 as an end point a at this time.

Oxygen Delivery/Consumption

Unlike the previously discussed end points of resuscitation, much literature has been devoted to the topic of oxygen delivery. Unfortunately, that literature produces a fair amount of confusion.

· When the body is in shock, there is inadequate delivery of oxygen to the tissues. As a result, there is a difference between baseline VO2 during health compared to the VO2 in shock – an oxygen debt. The cells need to make up for the time during which inadequate perfusion occurred (mismatch between O2 delivery and O2 demand during shock). Correcting this oxygen debt would imply adequate resuscitation. Because of the need to catch up, a logical conclusion is that elevating oxygen delivery to supranormal levels will help repay the oxygen debt.

CRITICAL O2 DELIVERY

OXYGEN CONSUMPTION

(VO2)

OXYGEN DELIVERY (DO2)

SHOCK STATE

NORMAL PHYSIOLOGIC STATE

OXYGEN DEBT

· In a number of studies, Shoemaker and colleagues found that critically ill surgical patients who survived had higher oxygen delivery and oxygen consumption. (19;20) (21). Survivors were seen to have attained:

Cardiac Index > 4.5 liters/min/ M2

Oxygen Delivery Index > 600 ml/min/ M2

Oxygen Consumption Index > 170 ml/min/ M2

It was then concluded that if critically ill surgical patients could have their oxygen delivery and consumption elevated to levels previously seen in survivors, survival for these patients could be improved.

· Shoemaker et al. found reduced complications, length of stay and mortality in high risk surgical patients brought preoperatively, intraoperatively, and postoperatively to the supranormal values above, compared to those treated to normal levels. (22) Similarly, Boyd et al. treated high-risk surgical patients to supranormal DO2, compared to conventional treatment, finding a reduction in mortality (5.7 vs. 22.2%) and complications (0.68/patient vs. 1.35/patients). (23) Most protocol patients were not able to reach goal DO2 values, although the values attained were significantly higher than those in the control group.

· Schiller et al. compared supranormal resuscitation in 30 burn patients to 50 patients with pulmonary artery catheters (PAC) not receiving hyperdynamic resuscitation, and to a 33 patient historical control group. (13) They found improved survival and a reduced incidence of multi-organ dysfunction syndrome (MODS) in the hyperdynamic group.

· After randomizing 26 septic patients to supranormal or normal resuscitation, Tuchsmidt et al. concluded that elevation of cardiac output and DO2 improves outcome. (24) Careful analysis reveals that there was actually a higher mortality in the optimal treatment (OT) group 72% vs. 50% in the nontreatment (NT) group. However, it was noted that some of the NT patients attained supranormal numbers and some of the OT patients did not attained target numbers. Data was then analyzed based on what values were reached, showing that survivors had higher cardiac performance indices. Therefore, this study simply revealed the higher values as markers of survival.

· A multi-center study, looking at 752 ICU patients, compared resuscitation to a normal cardiac index (2.5-3.5 l/min/M2) with resuscitation to a normal SvO2 (70%) or resuscitation to supranormal cardiac index (>4.5 L/min/ M2). (17) The authors found no difference in mortality between the three treatment groups. Even when further analysis was limited to patients that attained their target values, no differences were seen. Likewise, Yu and colleagues saw no difference when they treated septic, ARDS or hypovolemic patients to a hyperdynamic DO2I of 600 L/min/ M2 vs. more normal DO2I of 450-500 L/min/ M2. (25) Mortality rate was lower for a subgroup who reached supranormal levels whether treated or self-generated. Again, this shows attainment of certain values as a marker. Durham et al. were also unable to see a survival difference, as well as MODS difference, in 67 critically ill patients treated to conventional or hyperdynamic cardiac indices. (26) Heyland et al. then performed a meta-analysis of 7 studies concluding that interventions to achieve supranormal oxygen delivery did not convey a survival advantage. (27)

· Supranormal oxygen delivery as an end point of resuscitation remains controversial. Although a number of studies conclude that this strategy is not beneficial, it should be noted that these studies strive to push patients later in their course. Most of these studies are attempting to compare therapies instituted after significant organ dysfunction occurs. In addition, they include many different types of intensive care unit patients. Studies comparing therapies administered early to a defined group of patients in shock are needed before making a definitive conclusion regarding the efficacy of hyperdynamic resuscitation. It does appear to benefit high-risk surgical patients in the perioperative period.

Lactate

Metabolic indices may be helpful in determining adequacy or inadequacy of resuscitation. During aerobic metabolism, with the help of pyruvate dehydrogenase,

Pyruvate ® Acetyl CoA

producing 38 moles of adenosine triphosphate (ATP) per mole of pyruvate

However, during anaerobic metabolism, less efficient production of ATP takes place. Lactate dehydrogenase assists the following conversion:

Pyruvate ® Lactate

producing 2 moles of ATP per mole of pyruvate

All cells (except RBCs which lack mitochondria) can consume or remove lactate, either reducing lactate to glucose or oxidizing it to carbon dioxide and water. The liver and kidney cortex are the most important organs in lactate removal, accounting for 50% and 30% respectively. The Cori Cycle refers to the movement of lactate from peripheral tissues to liver/kidney for removal. Analysis of blood lactate (BL) thus provides a measure of the extent of global anaerobic metabolism.

Blood lactate appears to be a good marker not only for severity of the shock insult, but also for survival. In 1970, Weil and Afifi showed that BL correlated with cumulative oxygen debt and was a predictor for survival in animals as well as humans. (28) Dunham and colleagues demonstrated BL and base deficit (BD) as superior predictors for severity of hemorrhage and adequacy of resuscitation than BP and cardiac output. (29) Bakker et al. showed that BL better predicted outcome for septic shock patients than hemodynamic indices. (16) An observational study showed initial BL as a marker for 10-day survival in septic patients. (30)

Time is also a factor when considering lactate levels. For trauma patients, the longer the lactate is elevated, the more a patient is likely to develop MODS and die. (31) Bakker et al. discovered the same to be true for septic patients. (32) It is best to follow lactate levels over time rather than relying upon a single value. (33)

Some people have adopted the policy of elevating cardiac parameters as a means to clear lactate. Abramson et al. increased DO2 in 76 trauma patients until lactate was normal. (34) Clearance of lactate correlated with survival. In a randomized, controlled study, Boyd et al. showed improved survival in high-risk surgical patients treated with hyperdynamic means to decrease lactate pre, intra and postoperatively compared to conventional therapy. (23)

Multiple studies support the use of BL as an end point of resuscitation. Whether it comes from anaerobic metabolism, inhibition of pyruvate dehydrogenase or increased pyruvate production, lactate still correlates with survival. (8;16) This is also true in the presence of liver failure. (35) It appears that strategies utilizing cardiac parameters to clear lactate are appropriate, although more data is needed.

Base Deficit

· Base deficit (BD) can indirectly reflect blood lactate level. As has been stated, shock occurs when there is inadequate tissue oxygenation. This leads to lactic acidosis.

Base deficit is the amount of base (in mmoles) required to titrate 1 liter of whole blood to a pH of 7.4 (with 100% oxygen saturation and a PaCO2 of 40).

Therefore, the presence of a base deficit indicates an acidosis, resulting from fixed acids rather than hypercapnea. Unfortunately, it may reflect acidosis not related to elevated levels of lactate.

· Large amounts of data using goal directed, base deficit end points are not available. The initial advantage of base deficit was rapid laboratory results compared to blood lactate. However, newer technology allows lactate levels to be obtained in minutes. This is probably the major reason why base deficit has not been studied more intensely.

· In a retrospective study of 3791 trauma patients, Rutherford et al. found base deficit stratified mortality. (36) Davis et al. retrospectively evaluated almost 3000 trauma patients’ base deficit values, determining that admission values identified those likely to need transfusions. (3) One elaborate animal study found both base deficit and blood lactate to be superior to blood pressure and cardiac output as predictors of survival. (29) In fact, the combination of both BD and BL was superior to all other measures.

· One study, looking at 52 trauma patients, discovered no relationship between BL and BD or anion gap (AG). (37) Of note, BL did not get above 5 mmole/L. This is important based on other studies which reveal improved correlation of BL with AG as BL levels rise. Iberti et al. showed that 100% of surgical ICU patients with higher BL levels (>10 mmole/L) had AG’s greater than 16. (38) However, when BL was between 5 and 9.9 mmole/L, 50% of patients had an AG less than 16. When BL levels were less than 5 mmole/L, 79% of patients had AG’s less than 16. These results may explain why the first study did not show a BL and BD correlation. Davis et al. reported excellent correlation of BD and BL in a swine hemorrhagic model. (39) It should be noted that BL levels got up to 10 mmole/L with associated BD of 4.6 mmole/L.

· Base deficit is probably a good end point of resuscitation, however, studies are lacking. Base deficit is more likely to reflect BL levels in young trauma patients, early in their course. When other processes are present, which might contribute to an acidosis (i.e. hyperchloremia, renal failure), BD may not solely be due to elevated BL. When possible, a blood lactate should probably be performed in addition to the base deficit.

Gastric Mucosal pH (pHi)

· The metabolic measures discussed so far reflect global acidosis. The best measures of adequacy of resuscitation would reveal acidosis occurring at the tissue level. Because gastrointestinal mucosa represents one of the first areas from which blood is shunted during shock and one of the last to have it return after resuscitation, it provides an excellent resource for evidence of regional perfusion.

· Gastric mucosal pH (pHi) can be indirectly measured. (40) A nasogastric tube (NGT), equipped with a distal silicone balloon permeable to carbon dioxide (CO2), is placed in the usual fashion. The silicone balloon, filled with saline, is allowed to equilibrate within the stomach for 30-90 minutes. The saline is then withdrawn and sent along with arterial blood for analysis. After multiplying the saline PCO2 by a diffusion correction factor (supplied by manufacturer), and assuming that arterial blood gas HCO3 equals gastric HCO3, gastric mucosal pH is calculated using

Henderson-Hasselbach pHi = pKa – log (HCO3)/(PCO2)

Note that this technique also assumes that intramucosal PCO2 adequately equilibrates with intraluminal PCO2.

· Many gastric mucosal studies have been performed. Unfortunately, this adds to the confusion. These studies also suffer from the inadequacies of other studies mentioned previously (i.e. mixed ICU patient populations, timing, randomization issues, etc.). A number of observational studies in trauma patients, (4;41) septic patients (42;43) and mixed ICU patients (44) correlate lower pHi with increased mortality. Therefore, pHi appears to be a marker for survivability. The study by Oud and Haupt, though small, did find that patients may have normal hemodynamics as well as global acid-base balance, yet have abnormal gastric perfusion. (43)

· Ivatury et al. resuscitated 27 trauma patients to either normal pHi or a DO2 > 600 ml/min/ M2 and V02 > 150 ml/min/ M2. (45) Hyperdynamic indices did not correlate with pHi and no treatment was superior to the other. Gastric pH was significantly different in all survivors, no matter their treatment group. Ivatury et al. repeated this study with 57 trauma patients finding similar results this second time. (5) Once again, pHi appeared to be a marker for outcome. Perhaps comparing routine resuscitation to pHi-directed resuscitation would provide more useful data.

· Gomersall et al. increased oxygen delivery until a target pHi was reached or performed routine resuscitation in 210 mixed ICU patients, finding no difference. (46) Another mixed ICU patient study looked at routine versus pHi-directed resuscitation therapies in 260 patients. (47). In patients with an initial low pHi, treatment strategy made no difference. However, for those admitted with normal pHi, treatment to maintain pHi above a target value related to improved survival. These results go along with the argument that hyperdynamic resuscitation should be instituted early. Earlier therapy is more likely to make a difference than therapy initiated after organ dysfunction.

· At this point, measurement of pHi appears to be the best measure of regional perfusion, although its successful demonstration as an end point of resuscitation remains controversial. Problems include need for new equipment, long equilibration times (although new technology may supercede this limitation) and assumptions of arterial and mucosal HCO3 equality (some clinicians simply follow gastric PCO2 to avoid this). Although hundreds of studies have been performed, good randomized, controlled protocols performed in defined groups of ICU patients and instituted prior to significant organ dysfunction still need to be done. Global hemodynamics and acid-base may be normal when regional perfusion is not. Therefore, pHi needs to be substantiated as a legitimate end point.

Tissue Oxygen Levels

· The ultimate measure of adequacy of perfusion would evaluate cellular oxygen levels. A realistic measure today is that of tissue oxygenation. Hartmann et al. created stepwise hemorrhage in a swine model. (48) They compared groin transcutaneous oxygen levels (PtcO2) to thigh subcutaneous oxygen levels (SCO2) and pH levels at various gastrointestinal sites. PtcO2 was the earliest marker of hemorrhage, but all measurements correlated with oxygen transport indices. In a small study, using fiberoptic technology with a canine hemorrhage model, oxygen tension in muscle (PmO2) appeared to provide information similar to oxygen delivery and pH of muscle appeared to indicate adequacy of resuscitation. (49) Beilman et al. found near infrared measurements of regional tissue oxygenation correlated with global measurements in swine. (50) In 8 trauma patients resuscitated to hyperdynamic oxygen delivery, DO2 tracked with skeletal muscle oxygen tension both during and after resuscitation, but did not track SvO2 or pHi. (51)

· Tissue oxygenation remains a very promising end point of resuscitation. The minimally invasive nature of some of the technologies is additionally attractive. Unfortunately, further head to head comparisons with lactate, pHi and oxygen delivery are necessary before claiming this as the gold standard .

Venous Hypercarbia

· During early shock, a widening gradient is seen between arterial and venous carbon dioxide levels. With resuscitation, this gradient narrows. Ducey et al. were able to show a correlation between cardiac index and this gradient in hemorrhaged pigs. (52) Unfortunately, human studies are needed to substantiate this. An additional disadvantage is the need for invasive monitoring.

Summary

Successful resuscitation implies repaying the oxygen debt incurred during shock. Unfortunately, without knowing oxygen consumption levels prior to shock, oxygen debt is not known. Normal vitals signs may be present in the face of compensated shock and are not enough to tell us that we have adequately resuscitated our patient. Lack of full resuscitation can lead to systemic inflammatory response syndrome, multi-organ dysfunction syndrome and death. Many end points of resuscitation have yet to be proven. The best regional perfusion measure at present, gastrointestinal pH, is probably helpful, but remains controversial regarding its benefits and requires additional equipment. Until future technologies make tissue oxygen measurements uniformly available, base deficit and blood lactate appear to be our best means of determining how well we have resuscitated our patients.

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Notes: COMMENTS: Comment in: JAMA 1994 May 4; 271(17):1321; Comment in: ACP J Club 1994 May-Jun; 120 Suppl 3:76

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Notes: COMMENTS: Comment in: Chest 1993 Apr; 103(4):1311; discussion 1312; Comment in: Chest 1993 Apr; 103(4):1311-2; Comment in: Chest 1993 Apr; 103(4):1312

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Notes: COMMENTS: Comment in: Crit Care Med 1993 Jun; 21(6):815-7; Comment in: Crit Care Med 1994 Sep; 22(9):1512-3

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Notes: COMMENTS: Comment in: Crit Care Med 1997 Apr; 25(4):714-6

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35. Kruse JA, Zaidi SA, Carlson RW. Significance of blood lactate levels in critically ill patients with liver disease. Am J Med 1987 Jul;83(1): p77-82.

36. Rutherford EJ, Morris JA Jr, Reed GW, Hall KS. Base deficit stratifies mortality and determines therapy. J Trauma 1992 Sep;33(3): p417-23.

37. Mikulaschek A, Henry SM, Donovan R, Scalea TM. Serum lactate is not predicted by anion gap or base excess after trauma resuscitation. J Trauma 1996 Feb;40(2): p218-22; discussion 222-4.

38. Iberti TJ, Leibowitz AB, Papadakos PJ, Fischer EP. Low sensitivity of the anion gap as a screen to detect hyperlactatemia in critically ill patients [see comments]. Crit Care Med 1990 Mar;18(3): p275-7.

Notes: COMMENTS: Comment in: Crit Care Med 1991 Jan; 19(1):129-30; Comment in: Crit Care Med 1991 Jan; 19(1):130-1

39. Davis JW. The relationship of base deficit to lactate in porcine hemorrhagic shock and resuscitation [see comments]. J Trauma 1994 Feb;36(2): p168-72.

Notes: COMMENTS: Comment in: J Trauma 1994 Nov; 37(5):869-70

40. Melton A. Review of gastrointestinal tonometry and the early detection of gut ischemia. American Journal of Anesthesiology 2000;27(3):127-32.

41. Roumen RM, Vreugde JP, Goris RJ. Gastric tonometry in multiple trauma patients. J Trauma 1994 Mar;36(3): p313-6.

42. Friedman G, Berlot G, Kahn RJ, Vincent JL. Combined measurements of blood lactate concentrations and gastric intramucosal pH in patients with severe sepsis. Crit Care Med 1995 Jul;23(7): p1184-93.

43. Oud L, Haupt MT. Persistent gastric intramucosal ischemia in patients with sepsis following resuscitation from shock. Chest 1999 May;115(5): p1390-6.

44. Gutierrez G, Bismar H, Dantzker DR, Silva N. Comparison of gastric intramucosal pH with measures of oxygen transport and consumption in critically ill patients. Crit Care Med 1992 Apr;20(4): p451-7.

45. Ivatury RR, Simon RJ, Havriliak D, Garcia C, Greenbarg J, Stahl WM. Gastric mucosal pH and oxygen delivery and oxygen consumption indices in the assessment of adequacy of resuscitation after trauma: a prospective, randomized study. J Trauma 1995 Jul;39(1): p128-34; discussion 134-6.

46. Gomersall CD, Joynt GM, Freebairn RC, Hung V, Buckley TA, Oh TE. Resuscitation of critically ill patients based on the results of gastric tonometry: a prospective, randomized, controlled trial. Crit Care Med 2000 Mar;28. 28(3. 3):607-14.

47. Gutierrez G, Palizas F, Doglio G, Wainsztein N, Gallesio A, Pacin J, Dubin A, Schiavi E, Jorge M, Pusajo J, et al. Gastric intramucosal pH as a therapeutic index of tissue oxygenation in critically ill patients [see comments]. Lancet 1992 Jan 25;339(8787): p195-9.

Notes: COMMENTS: Comment in: Lancet 1992 Feb 29; 339(8792):550-1; Comment in: Lancet 1992 May 2; 339(8801):1123-4

48. Hartmann M, Montgomery A, Jonsson K, Haglund U. Tissue oxygenation in hemorrhagic shock measured as transcutaneous oxygen tension, subcutaneous oxygen tension, and gastrointestinal intramucosal pH in pigs [see comments]. Crit Care Med 1991 Feb;19(2): p205-10.

Notes: COMMENTS: Comment in: Crit Care Med 1991 Feb; 19(2):141-3

49. McKinley BA, Parmley CL, Butler BD. Skeletal muscle PO2, PCO2, and pH in hemorrhage, shock, and resuscitation in dogs. J Trauma 1998 Jan;44. 44(1. 1):119-27.

50. Beilman GJ, Groehler KE, Lazaron V, Ortner JP. Near-infrared spectroscopy measurement of regional tissue oxyhemoglobin saturation during hemorrhagic shock. Shock 1999 Sep;12. 12(3. 3):196-200.

51. McKinley BA, Marvin RG, Cocanour CS, Moore FA. Tissue hemoglobin O2 saturation during resuscitation of traumatic shock monitored using near infrared spectrometry. J Trauma 2000 Apr;48. 48(4. 4):637-42.

52. Ducey JP, Lamiell JM, Gueller GE. Arterial-venous carbon dioxide tension difference during severe hemorrhage and resuscitation [see comments]. Crit Care Med 1992 Apr;20. 20(4. 4):518-22.

Notes: COMMENTS: Comment in: Crit Care Med 1994 Jun;22(6):1064

[Ace844]

(Trauma Patients Receiving CPR: Predictors of Survival.(cardiopulmonary resuscitation). Denise L. Garee.

Journal of Trauma Nursing 12.3 (July-Sept 2005): p89(1).

Subjects

Full Text :COPYRIGHT 2005 Nursecom @ Inc.

Pickens, J., Copass, M., Bulger, E. The Journal of Trauma Injury, Infection and Critical Care, 2005, 58(5): 951-958

Denise L. Garee, MSN, RN)

INTRODUCTION: The objective of the study was to test recent NAEMSP and ACSCOT guidelines (2003) regarding cessation of resuscitative efforts of pre-hospital providers for patients suffering traumatic cardiopulmonary arrest (TCPA) and determine if pre-hospital assessments using clinical criteria were associated with the survival of those having TCPA. The EMS system studied was tiered; having both ALS and BLS responders.

ABSTRACT: A retrospective study using trauma registry data (n= 173) and the Seattle FD database (n=93) on trauma patients transferred to the level 1 center, taken from 1994-2001 were reviewed. The cohort total was 266 with 82 excluded from the final study analysis mostly (n=41) for not needing CPR upon initial assessment of SFD personnel. The majority of the trauma victims were male, with a mean age of 38 for non-survivors and 36 for survivors. The highest percentage of non-survivor injury was related to GSW and blunt trauma; 41.8% of non-survivors (n=170) were multiple trauma victims, as were 42.9% of survivors. Of 184 patients in the study, 14 (7.6%) survived to discharge, SFD determined 46 of them DNR after assessment at the scenes, with 138 (75%) being transferred to the level 1 facility. Assessment findings strongly associated with survival were, pulse >40, respiratory effort, + pupil reactivity, GCS >3, RTS >0 and an ISS score <25. However, the only independent predictor of survival was an EKG rate of >40. With the exception of intubation, ACLS invasive and medication interventions were not associated with survival. Non-survival factors included type of injury (88% of deaths had head or high cervical spine injury), the need for defibrillation upon arrival to the ED (n=38), CVP placement in the ED, and those receiving ACLS drugs during resuscitation in the ED, (>97% with 77.2% declared dead in the ED). The researchers also found that once a pulse was established in the field, further intervention in the ED was unnecessary, and triage to a definitive care area (OR), was more important than either pre-hospital or ED level care. When comparing the assessment findings to the guidelines, the researchers found had the guidelines been strictly adhered to, 93% of the survivors would not have been resuscitated secondary to the on-scene and transport time element.

The researchers noted several problems with data analysis, mostly relating to documentation omissions by pre-hospital care providers. They also found that ALS and BLS responders did not agree on the initial assessment of the victim, and that ALS assessment ability varied, and was not always accurate when comparing initial ED assessments with last ALS assessments. (13 References)

COMMENTARY: The discrepancies found in the assessment abilities of both BLS and ALS providers can be related to educational background and experience. However it does call into question whether BLS personnel are equipped to appropriately triage and determine whether CPR is necessary, should be withheld, or terminated. The researchers did reflect previous research done on specifics, however noted they were the first to critically look at the differences of the pre-hospital responders. It is not surprising to find intubation assisted the high percent of the survivors, as airway maintenance is always a priority and lack of a definitive airway will lead to demise, nor is it surprising to find that the presence of a pulse was a predictor for survival. Additionally it is no surprise that operative intervention is key to the survivability of the trauma victim, and rapid triage in the ED upon arrival and transport to the OR are the mainstay of treatment for multiple trauma victims. What the authors failed to mention was the guidelines are just that, guidelines and should not preclude assessor judgment. The authors suggest the guidelines not be instituted until further investigation into their effectiveness has been established, however, when looking at the guidelines, they are logical and may assist with decreasing the number of patients received by trauma centers where treatment would be futile.

Denise L. Garee MSN, RN, is the Emergency Clinical Nurse Specialist at New Hanover Health Network, in Wilmington, NC.

.

[Ace844]

(Thrombolytic therapy in patients requiring cardiopulmonary resuscitation. Alan N. Tenaglia @ Robert M. Califf, Richard J. Candela, Dean J. Kereiakes, Eric Berrios, Sharon Y. Young, Richard S. Stack and Eric J. Topol.

American Journal of Cardiology v68.n10 (Oct 15, 1991): pp1015(5).)

Abstract:

Thrombolytic (clot-breaking) therapy is a new form of treatment given to patients soon after a heart attack has occurred, and significantly decreases the death rate associated with attacks. However, patients who have needed some type of cardiopulmonary resuscitation (CPR) due to arrest of heart function are generally excluded from thrombolysis because of possible adverse effects of the treatment. However, patients who need CPR are at high risk even when given conservative therapy and may have the most to gain from thrombolysis. This issue was evaluated in a study of 59 patients who received less than 10 minutes of CPR before thrombolysis or those who required CPR within six hours of therapy. These patients were part of a group of 708 patients who were enrolled in a study of thrombolysis. CPR techniques included chest compression, defibrillation, or other interventions in response to heart arrhythmias or circulatory instability. In patients who had CPR, the front portion of the heart was more often involved. The rate of death occurring in the hospital was somewhat higher in the CPR group, and all deaths occurred among the 22 patients who required resuscitation measures beyond defibrillation (prolonged CPR group). The rate of cardiac complications was similar in CPR and non-CPR groups, while the prolonged CPR group had a higher rate of further cardiac arrests, hypotension (low blood pressure), pulmonary edema (lung congestion), and coma. No complications attributable to CPR were found, and the rate of bleeding complications was similar. The study suggests that patients who receive CPR for less than 10 minutes following a heart attack can safely receive thrombolytic therapy and may particularly benefit from the treatment. (Consumer Summary produced by Reliance Medical Information, Inc.)

(Efficacy and safety of thrombolytic therapy after initially unsuccessful cardiopulmonary resuscitation: a prospective clinical trial. Bernd W Bottiger @ Christoph Bode, Sabine Kern, Andre Gries, Rene Gust, Rolf Glatzer, Harald Bauer, Johann Motsch and Eike Martin.

The Lancet 357.9268 (May 19, 2001): p1583.)

Abstract:

The authors report on an investigative trial to determine if thrombolytic therapy combined with heparin, which has been shown to be of benefit during cardiopulmonary resuscitation (CPR), would be beneficial to people after a heart attack in whom CPR had not been successful. They found a significant enough improvement in circulation and survival to justify a large scale controlled trial.

Full Text :COPYRIGHT 2001 The Lancet Ltd.

Summary

Background During cardiopulmonary resuscitation (CPR), thrombolysis can help to stabilise patients with pulmonary embolism and myocardial infarction. Moreover, thrombolysis during CPR has beneficial effects on cerebral reperfusion after cardiac arrest. We investigated this new therapeutic approach in patients in whom conventional CPR had been unsuccessful.

Methods We assessed, in a prospective study, patients undergoing CPR after out-of-hospital cardiac arrest for cardiological reasons in whom return of spontaneous circulation was not achieved within 15 min. According to the Ustein criteria, our control group consisted of patients who were assessed during 1 year. After this year patients were treated with a bolus of 5000 U of heparin and 50mg, over 2 min, of tissue-type plasminogen activator (rt-PA treated group). This intervention was repeated if return of spontaneous circulation was not achieved within the following 30 min. For controls only CPR was given.

Findings Overall, 90 patients were included; heparin and rt-PA were given to 40 patients. There were no bleeding complications related to the CPR procedures. Of the rt-PA group, 68% (27) had return of spontaneous circulation and 58% (23) were admitted to a cardiac intensive care unit, compared with 44% (22; p=0.026) and 30% (15; p=0.009) of the controls, respectively. At 24 h after cardiac arrest a larger proportion of the rt-PA group than of the controls was alive (35% [14] vs 22% [11], p=0.171), and 15% (six) of rt-PA-treated patients and 8% (four) of controls could be discharged from hospital.

Interpretation After initially unsuccessful out-of-hospital CPR, thrombolytic therapy combined with heparin is safe and might improve patient outcome. On the basis of our data a randomised controlled trial might be regarded as ethical.

Lancet 2001; 357: 1583-85

see page

Introduction

The outlook of patients who have had out-of-hospital cardiac arrest is generally poor, and few specific treatments are available.(1,2)

In about 50% to more than 70% of patients who had to be resuscitated after out-of-hospital cardiac arrest, either acute myocardial infarction or massive pulmonary embolism--and, thus, intravascular thrombosis--is the cause of the cardiocirculatory arrest.(3,4) Although cardiac arrest that is initiated by intracoronary thrombosis is quite different from pulmonary embolism, thrombolysis is an effective strategy in both.(5,6) However, thrombolytic therapy during cardiopulmonary resuscitation (CPR) has traditionally been contraindicated because of the fear of severe bleeding complications associated with CPR procedures.

Findings from clinical case reports and small case series suggest that thrombolysis during CPR can contribute to haemodynamic stabilisation and long-term survival in patients with cardiac arrest after acute myocardial infarction or massive pulmonary embolism.(7-11) Moreover, an unusual proportion of patients described in these reports survived long periods of cardiac arrest and CPR without any, or only minor, neurological deficits.(7,12) This survival might be attributable to the fact that, after cardiac arrest, reperfusion is associated with a striking and disseminated intravascular activation of blood coagulation without adequate activation of endogenous fibrinolysis and, thus, with intravascular clotting and fibrin formation.(13-15) Therefore, thrombolysis during CPR, besides addressing the cause of acute myocardial infarction and pulmonary embolism, could also lead to a general improvement in microcirculatory flow, including cerebral reperfusion.(14,16) Experimental data indicate that thrombolysis during CPR improves early cerebral microcirculatory reperfusion,(14,17) and that thrombolytic agents directly affect cerebral tolerance to ischaemia.(18) Therefore, our aim was to determine prospectively whether thrombolytic therapy is safe and effective after unsuccessful CPR out of hospital.

Methods

Patients

After institutional approval, we investigated in accordance with the Utstein Consensus Conference criteria,(19) patients undergoing CPR after out-of-hospital cardiac arrest of cardiac aetiology in an area with advanced cardiac life-support service system staffed by doctors. The ethics committee approved the protocol for an intervention trial and deemed informed consent unnecessary. However, random assignment of unconscious patients was not approved for ethical and legal reasons. We obtained informed consent post hoc, for data acquisition and analysis, from patients who survived without neurological damage, as well as assent from patients' relatives. Inclusion criteria were: age 18-75 years, no minor or major trauma, no indication of any internal or external bleeding, and no return of spontaneous circulation within 15 min of conventional CPR procedures. Patients with asystole on initial electrocardiogram during CPR were not excluded. Each emergency doctor was aware of inclusion and exclusion criteria and enrolled appropriate patients. Assessment of cardiac arrest and CPR was done in accordance with guidelines of the American Heart Association1 and the European Resuscitation Council.(20)

Interventions

Outcome without specific intervention was assessed during a 1 year period (control group). After this year, all patients who fulfilled the inclusion criteria were additionally treated with a bolus of 5000 U of heparin and 50 mg of tissue-type plasminogen activator (rt-PA) given intravenously over 2 min after 15 min of unsuccessful CPR (rt-PA group). If return of spontaneous circulation was not achieved within the following 30 min they received a further 5000 U of heparin and 50 mg of rt-PA. There were no other changes in the resuscitation protocols. Controls were patients who had only CPR. In this group, CPR was given initially for 15 min, and if there was no return of spontaneous circulation, patients received further CPR. Primary endpoints were safety of the protocol (ie, absence of CPR related bleeding complications), return of spontaneous circulation, and admission to a cardiac intensive care unit. Secondary endpoints were 24 h survival and hospital discharge. The ethics committee requested an interim analysis of safety and efficacy of the intervention after enrolment of 20 and 40 patients in the rt-PA group, respectively.

We did statistical analysis (SPSS, version 6.0) with logistic regression and x2, Wilcoxon's, and t tests. A p value less than 0.05 was deemed significant.

Results

Overall, 90 patients were enrolled: 50 were controls, and 40 patients were given heparin combined with rt-PA. There were no differences between the two groups with respect to age, sex, number of cardiac arrests witnessed by bystanders, interval between alarm and arrival of advanced cardiac life-support unit, initial cardiac rhythm, duration of CPR in patients with return of spontaneous circulation, and number who had electrical defibrillation (table). Complications due to bleeding that required transfusion of packed red blood cells were seen in two patients (both in the rt-PA group; p=0.379 vs controls). Of these patients, one needed transfusion of two units because of internal bleeding from a gastric ulcer 12 days after cardiac arrest. In the second patient, gastric ulcer bleeding required transfusion of four units 2 days after cardiac arrest. Despite long resuscitation procedures, no bleeding complications related to CPR were recorded.

Controls rt-PA

(n=50) (n=40)

Age (years)[*] 61 (11) 64 (10)

Men 37 (74%) 27 (68%)

Bystander witnessed cardiac arrest 33 (66%) 26 (65%)

Time between alarm and arrival of 8 (5) 9 (4)

ALS unit (min)[*]

Initial cardiac rhythm during CPR

Asystole 28 (56%) 21 (53%)

Ventricular fibrillation/VT 16 (32%) 15 (37%)

Other cardiac rhythms 6 (12%) 4 (10%)

Electrical defibrillation 35 (70%) 30 (75%)

Duration of CPR in patients with ROSC (min)[*] 37 (22) 40 (23)

p

Age (years)[*] 0.133

Men 0.499

Bystander witnessed cardiac arrest 0.921

Time between alarm and arrival of 0.109

ALS unit (min)[*]

Initial cardiac rhythm during CPR

Asystole 0.740

Ventricular fibrillation/VT 0.585

Other cardiac rhythms 0.764

Electrical defibrillation 0.599

Duration of CPR in patients with ROSC (min)[*] 0.328

ALS=advanced cardiac life support; CPR=cardiopulmonary resuscitation;

ROSC=return of spontaneous circulation; rt-PA=recombinant tissue-type

plasminogen activator; VT=ventricular tachycardia. [*] Mean (SD).

Characteristics of patients

In the rt-PA group, return of spontaneous circulation was achieved in 68% (27) of patients and 58% (23) were admitted to a cardiac intensive-care unit, compared with 44% ([22], p=0.026) and 30% ([15], p=0.009) of controls, respectively. At 24 h after cardiac arrest 35% (14) of rt-PA-treated patients compared with 22% (11) of controls, were still alive (p=0.171), and 15% (six) of rt-PA treated patients compared with 8% (four) of controls were discharged (figure). Compared with standard therapy, the odds ratio of return of spontaneous circulation was 2.65 (95% CI 1.11-6.25) and that of intensive care unit admission was 3.15 (1.32-7.69) if patients were treated with heparin and rt-PA during CPR. Logistic regression analysis for all numeric variables (age, time interval between alarm and arrival of the advanced cardiac life-support unit, and duration of CPR) showed that the effects of these indices did not differ between groups.

[GRAPH OMITTED]

Discussion

Our data show that, after initially unsuccessful out-of-hospital CPR thrombolytic therapy combined with heparin is feasible and safe. Thrombolytic therapy during CPR did not cause CPR-related bleeding complications. Additionally, this therapeutic strategy seems effective in improving outcome. The number of patients with return of spontaneous circulation and of those who could be admitted to a cardiac intensive-care unit was substantially higher in the rt-PA group. Hospital discharge rate was nearly doubled in patients treated with rt-PA, but because the study was too small we could not draw conclusions in this respect.

One of our most important findings was the safety of thrombolytic therapy during CPR. Both complications due to bleeding in the rt-PA group were upper gastrointestinal haemorrhage, which occurred on days 2 and 12 after rt-PA treatment. Therefore, whether these complications were causally related to administration of thrombolytic agents is questionable. There were no CPR-related bleeding complications, which is in accordance with almost all published case reports and case series of thrombolysis during CPR in patients with acute myocardial infarction or pulmonary embolism.(7-12) Because of the concern of important bleeding complications in patients who could be stabilised without thrombolytic therapy, only patients with initially unsuccessful CPR and, thus, a subgroup with a poor outlook(21) were enrolled. Therefore, the possibility cannot be ruled out that the effect of heparin and rt-PA treatment will be even more pronounced if this intervention is done immediately after the initiation of CPR.

For ethical reasons, the ethics committee did not approve random assignment of unconscious patients. Therefore, we did a prospective intervention study and compared two groups of patients with identical inclusion criteria. Controls and patients treated with rt-PA were closely similar with respect to several important factors. Therefore, relevant factors known to affect survival after out-of-hospital cardiac arrest22 were not different between the two groups. The ethics committee requested an interim analysis in the rt-PA group. Therefore, the trial was stopped after the second interim analysis because of a substantial improvement in early patient outcome with heparin and rt-PA. Because we did not note any significant differences in bleeding complications between the groups we believe that thrombolysis during CPR can now be assessed in a randomised controlled trial.

The present therapeutic regimen focuses on two pathophysiologically relevant issues in cardiac arrest patients. First, it acts locally at the site of arterial thrombosis or thromboembolism in patients with acute myocardial infarction and pulmonary embolism and, thus, the underlying pathology can be affected very quickly.(5,6,23) We know that thrombolysis during CPR can lead to haemodynamic stabilisation in these conditions.(7-12) Furthermore, the outlook in patients with cardiac arrest associated with acute myocardial infarction, and who were treated with thrombolytic agents after return of spontaneous circulation, is better than that in patients after cardiac arrest who did not receive such treatment.(24) Therefore, patients with myocardial infarction requiring CPR might profit more from thrombolysis than those who do not have cardiac arrest. Further, heparin and rt-PA promote general improvement in microcirculatory reperfusion,(14,17,25,26) and there is a positive effect of rt-PA on cerebral tolerance to ischaemia.(18) Experimental and clinical studies have shown that cardiocirculatory arrest and CPR are associated with a striking activation of blood coagulation, without adequate activation of endogenous fibrinolysis.(13-15) Therefore, intravascular fibrin formation and microthromboses are distributed throughout the entire microcirculation after cardiac arrest.(13,15,27,28) In accordance with this finding, heparin, thrombolytic agents, or both are associated with an immediate improvement in cerebral microcirculatory reperfusion; an improvement in myocardial contractility; and an increase in the survival rate after experimentally induced cardiac arrest.(17,25,26,29-31)

Thrombolysis seems to act very quickly in these serious situations. This quick response might be due to the specific fibrinolytic action combined with non-specific fibrinogenolysis, leading to an immediate and generalised improvement in microcirculatory reperfusion, which might be important during CPR when proper circulation does not exist.(9,13,17,26) Our study shows that this new therapeutic option is safe and can be successfully applied clinically. A limitation of our study is the absence of proper randomisation. However, our data lend support to the possibility of improved outcome with thrombolysis during CPR. Thrombolytic therapy combined with heparin after initially unsuccessful out-of-hospital CPR is safe and seems to improve patient outcome. Therefore, a randomised controlled trial that focuses on that treatment strategy might now be ethical.

Contributors

B W Bottiger and C Bode initiated the study. B W Bottiger, C Bode, S KErn, A Gries, R Gust, R Glatzer, H Bauer, J Motsch, and E Martin designed the study, obtained the data, assessed outcomes, and wrote and edited the paper. B W Bottiger and J Motsch coordinated the study. H Bauer did statistical analysis.

Acknowledgments

We thank C Herfarth and W Kubler for their support. B W Bottiger was supported by the Deutsche Forschungsgemeinschaft (DFG; BO 1686/1-1) and by a grant from the medical faculty of the University of Heidelberg (no 345/1999).

Departments of Anaesthesiology (B W Bottiger MD, S Kern MD, A Gries MD, R Gust MD, R Glatzer MD, H Bauer MD, J Motsch MD, E Martin MD) and Internal Medicine (C Bode MD), University of Heidelberg, D-69120 Heidelberg, Germany; and Department of Internal Medicine, University of Freiburg, Freiburg (C Bode)

Correspondence to: Dr Bernd W Bottiger

(e-mail: bernd_boettiger@med.uni-heidelberg.de)

References

(1) Emergency Cardiac Care Committee and Subcommittees AHA. Guidelines for cardiopulmonary resuscitation and emergency cardiac care. JAMA 1992; 268: 2171-298.

(2) Kudenchuk PJ, Cobb LA, Copass MK, et al. Amiodarone for resuscitation after out-of-hospital cardiac arrest due to ventricular fibrillation. N Engl J Med 1999; 341: 871-78.

(3) Silfvast T. Cause of death in unsuccessful prehospital resuscitation. J Intern Med 1991; 229: 331-35.

(4) Spaulding CM, Joly LM, Rosenberg A, et al. Immediate coronary angiography in survivors of out-of-hospital cardiac arrest. N Engl J Med 1997; 336: 1629-33.

(5) Bode C, Nordt TK, Runge MS. Thrombolytic therapy in acute myocardial infarction--selected recent developments. Ann Hematol 1994; 69: S35-40.

(6) Goldhaber SZ, Kessler CM, Heit JA, et al. Recombinant tissue-type plasminogen activator versus a novel dosing regimen of urokinase in acute pulmonary embolism: a randomized controlled multicenter trial. J Am Coll Cardiol 1992; 20: 24-30.

(7) Bottiger BW. Thrombolysis during cardiopulmonary resuscitation. Fibrinolysis 1997; 11 (suppl 2): 93-100.

(8) Bottiger BW, Bohrer H, Bach A, Motsch J, Martin E. Bolus injection of thrombolytic agents during cardiopulmonary resuscitation for massive pulmonary embolism. Resuscitation 1994; 28: 45-54.

(9) Bottiger BW, Reim SM, Diezel G, Bohrer H, Martin E. High-dose bolus injection of urokinase; use during cardiopulmonary resuscitation for massive pulmonary embolism. Chest 1994; 106: 1281-83.

(10) Langdon RW, Swicegood WR, Schwartz DA. Thrombolytic therapy of massive pulmonary embolism during prolonged cardiac arrest using recombinant tissue-type plasminogen activator. Ann Emerg Med 1989; 18: 678-80.

(11) Tiffany PA, Schultz M, Steuven H. Bolus thrombolytic infusions during CPR for patients with refractory arrest rhythms: outcome of a case series. Ann Emerg Med 1998; 31: 124-26.

(12) Newman DH, Greenwald I, Calleway CW. Cardiac arrest and the role of thrombolytic agents. Ann Emerg Med 2000; 35: 472-80.

(13) Bottiger BW, Motsch J, Bohrer H, et al. Activation of blood coagulation after cardiac arrest is not balanced adequately by activation of endogenous fibrinolysis. Circulation 1995; 92: 2572-78.

(14) Fischer M, Bottiger BW, Popov-Cenic S, Hossmann KA. Thrombolysis using plasminogen activator and heparin reduces cerebral no-reflow after resuscitation from cardiac arrest: an experimental study in the cat. Intensive Care Med 1996; 22: 1214-23.

(15) Gando S, Kameue T, Nanzaki S, Nakanishi Y. Massive fibrin formation with consecutive impairment of fibrinolysis in patients with out-of-hospital cardiac arrest. Thromb Haemost 1997; 77: 278-82.

(16) Fischer M, Hossmann KA. No-reflow after cardiac arrest. Intensive Care Med 1995; 21: 132-41.

(17) Lin SR, O'Connor MJ, Fischer HW, King A. The effect of combined Dextran and streptokinase on cerebral function and blood flow after cardiac arrest: an experimental study on the dog. Invest Radiol 1978; 13: 490-98.

(18) Kim YH, Park JH, Hong SH, Koh JY. Nonproteolytic neuroprotection by human recombinant tissue plasminogen activator. Science 1999; 284: 647-50.

(19) Cummins RO, Chamberlain DA, Abramson NS, et al. Recommended guidelines for uniform reporting of data from out-of-hospital cardiac arrest: the Utstein style. Circulation 1991; 84: 960-75.

(20) European Resuscitation Council. Guidelines for basic and advanced life support. Resuscitation 1992; 24: 103-21.

(21) Fischer M, Fischer NJ, Schuttler J. One-year survival after out-of-hospital cardiac arrest in Bonn city: outcome report according to the 'Utstein style'. Resuscitation 1997; 33: 233-43.

(22) Bottiger BW, Grabner C, Bauer H, et al. Long term outcome after out-of-hospital cardiac arrest with physician staffed emergency medical services: the Utstein style applied to a midsized urban/suburban area. Heart 1999; 82: 674-79.

(23) Scholz KH, Tebbe U, Herrmann C, et al. Frequency of complications of cardiopulmonary resuscitation after thrombolysis during acute myocardial infarction. Am J Cardiol 1992; 69: 724-28.

(24) Schiele R, Rustige J, Burcyk U, et al. Thrombolysis after resustication in acute myocardial infarction. J Am Coll Cardiol 1996; 27 (suppl a): 279A.

(25) Darius H, Yanagisawa A, Brezinski ME, Hock CE, Lefer AM. Beneficial effects of tissue-type plasminogen activator in acute myocardial ischemia in cats. J Am Coll Cardiol 1986; 8: 125-31.

(26) Safar P, Xiao F, Radobsky A, et al. Improved cerebral resuscitation from cardiac arrest in dogs with mild hypothermia plus blood flow promotion. Stroke 1996; 27: 105-13.

(27) Hartveit F, Halleraker B. Intravascular changes in kidneys and lungs after external cardiac massage: a preliminary report. J Pathol 1970; 102: 54-58.

(28) Hekmatpanah J. Cerebral blood flow dynamics in hypotension and cardiac arrest. Neurology 1973; 23: 174-80.

(29) Crowell JW, Sharpe GP, Lambright RL, Read WL. The mechanism of death after resuscitation following acute circulatory failure. Surgery 1955; 38: 696-702.

(30) Crowell JW, Smith EE. Effect of fibrinolytic activation on survival and cerebral damage following periods of circulatory arrest. Am J Physiol 1956; 186: 283-85.

(31) Gaszynski W. The use of protease inhibitor (Trasylol) and heparin in cardiorespiratory resuscitation. I. Studies of the blood clotting system. Anaesth Resus Inten Therap 1975; 3: 125-34.

[Mikeyg]

I would run the code.

my 2 cents.

[Ace844]

Another potential use for your defibrillator during CPR??? Interesting article for you all to read.

(Thoracic impedance changes measured via defibrillator pads can monitor ventilation in critically ill patients and during cardiopulmonary resuscitation*

Heidrun Losert @ MD; Martin Risdal, MSc; Fritz Sterz, MD, PhD; Jon Nysæther, PhD; Klemens Köhler, MD;

Trygve Eftestøl, PhD; Cosima Wandaller, MD; Helge Myklebust, BEng; Thomas Uray, MD;

Gottfried Sodeck, MD; Anton N. Laggner, MD, PhD)

Recent reports (1–4) discussed

the suboptimal quality of cardiopulmonary

resuscitation

(CPR) (5). Aufderheide et al. (4)

demonstrated that rescuers consistently

tend to hyperventilate out-of-hospital cardiac

arrest patients. Karlsson et al. (6) stated

that in their pig model, increased tidal volumes

and hypocarbia were known to develop

and adversely affect cardiac output. Dorph et

al. (7) suggested a tidal volume of 10 mL/kg

delivered three times per minute during CPR

to achieve normocapnia, and Baskett et al.

(8) found that the tidal volume perceived to

achieve chest rise was on the order of 300–

500 mL. Wik et al. (9) demonstrated that a

too short inspiration time was a common

problem in a manikin model where emergency

medical service personnel delivered

mouth-to-mouth ventilations.

The possibility for measuring ventilation

rate, tidal volume, and inspiration

time based on thorax impedance changes

has long been known (10, 11). Pellis et al.

(12) measured ventilations in pigs by thorax

impedance through defibrillator pads.

Those authors suggested that the same

method can be used to monitor human

ventilation activity during resuscitation.

The preceding findings highlight the

need for continuous ventilation monitoring

during CPR, even if debate continues

as to whether ventilation is indeed required

in addition to uninterrupted chest

compression (5). In manikin studies it

was found that such monitoring would

improve the efficacy of CPR. Wik et al. (9)

presented this effective method for CPR

training. Handley et al. (13) suggested

that if a feedback system is incorporated

into an automatic external defibrillator

(AED), this could lead to a better performance

of CPR. Therefore, the concept of

measuring thoracic impedance via defibrillator

pads in patients to guide CPR is

*See also p. xx.

From Department of Emergency Medicine, Medical

University of Vienna, Austria (HL, FS, KK, CW, TU, GS,

ANL); Department of Electrical and Computer Engineering,

University of Stavanger, Norway (MR, TE); and

Laerdal Medical, Stavanger, Norway (JN, HM).

Helge Myklebust and Jon Nysæther are Laerdal Medical

Employees. Klemens Köhler was employed for 12

months at the Department of Emergency Medicine, Medical

University Vienna with support of a grant from Laerdal

Medical, Stavanger, Norway. Laerdal Medical, Stavanger,

Norway provided travel grants for scientific meetings for

Heidrun Losert and Klemens Köhler. Heartstart 4000SP

with the necessary analysis software was provided by

Laerdal Medical. Heidrun Losert received a laptop from

Laerdal Medical, Stavanger, Norway. The study was supported

in part by a commercial sponsor (Laerdal Medical,

Stavanger, Norway). Non-Laerdal employees had unrestricting

editing rights, so that the manuscript was as free

from corporate bias as possible. The sponsor could not

have suppressed publication if the results were negative

or detrimental to the product they produce.

Copyright © 2006 by the Society of Critical Care

Medicine and Lippincott Williams & Wilkins

DOI: 10.1097/01.CCM.0000235666.40378.60

Objective: Monitoring of ventilation performance during cardiopulmonary

resuscitation would be desirable to improve the quality of

cardiopulmonary resuscitation. To investigate the potential for measuring

ventilation rate and inspiration time, we calculated the correlation

in waveform between transthoracic impedance measured

via defibrillator pads and tidal volume given by a ventilator.

Design: Clinical study.

Setting: Emergency department of a tertiary care university

hospital.

Patients: A convenience sample of mechanical ventilated patients

(n _ 32), cardiac arrest patients (n _ 20), and patients

after restoration of spontaneous circulation (n _ 31) older than 18

from an emergency department of a tertiary care university hospital

were eligible. In many of the latter patients, cardiac arrest

data could not be obtained.

Interventions: The Heartstart 4000SP defibrillator (Laerdal

Medical Cooperation, Stavanger, Norway) with additional capabilities

of recording thoracic impedance changes was used.

Measurements and Main Results: The relationship between

impedance change and tidal volume (impedance coefficient) was

calculated. The mean (SD) correlations between the impedance

waveform and the tidal volume waveform in the patient groups

studied were .971 (.027), .969 (.032), and .967 (.035), respectively.

The mean (SD) impedance coefficient for all patients in the study

was .00194 (.0078) _/mL, and the mean (SD) specific (weightcorrected)

impedance coefficient was .152 (.048) _/kg/mL. The

measured thorax impedance change for different tidal volumes

(400–1000 mL) was approximately linear.

Conclusions: The impedance sensor of a defibrillator is accurate

in identifying tidal volumes, when chest compressions are

interrupted. This also allows quantifying ventilation rates and

inspiration times. However this technology, at its present state,

provides only limited practical means for exact tidal volume

estimation. (Crit Care Med 2006; 34:●●●–●●●)

KEY WORDS: cardiopulmonary resuscitation; defibrillation; heart

arrest; impedance; monitoring; ventilation

Crit Care Med 2006 Vol. 34, No. 9 1

practically important in the settings of

out-of-hospital cardiac arrest.

The aim of our study was to investigate

the potential of using impedance measurements

for quantifying tidal volume using

defibrillator pads in the standard lead II

position on a convenience sample of ventilated

patients (reference ventilated patients,

full cardiac arrest patients, and patients after

restoration of spontaneous circulation).

Estimates of the impact of alternative electrode

pad placement on the accuracy of

assessment of respiratory rate, inspiratory

time, and tidal volume are also reported.

METHODS

Study Design

This was a prospective, observational case

series of a convenience sample of ventilated

emergency department patients between December

2003 and March 2005. The study procedures

were in accordance with the ethical

standards of the Medical University of Vienna

and approved by the responsible committee on

human experimentation at university.

Setting

The study was carried out at an emergency

department of a tertiary care university hospital

with an annual census of 75,000 patients.

Participants

A convenience sample of endotracheally intubated

patients _18 yrs of age in hemodynamically

stable, controlled mechanically ventilated

conditions (reference group) were

eligible for entry into this study. To evaluate

our findings, we further tested patients suffering

a nontraumatic, normothermic, witnessed

cardiopulmonary arrest (cardiac arrest group).

The latter were also studied during times of

restoration of spontaneous circulation (ROSC

group). Patients were not included if they had

known terminal conditions, pregnancy, or

contraindications for high peak pressure ventilation,

such as patients with chronic obstructive

pulmonary disease or asthma, cerebral

bleeding, or insult (Table 1).

Intensive care medicine such as controlled

mechanical ventilation and/or advanced cardiac

life support was provided according to a

standard protocol (14, 15). Admission diagnosis

and known medical history were routinely

assessed, and the data for cardiac arrest patients

encompassed all information required

for the international Utstein-style criteria

(16). Medications given were evaluated, and

chest radiograph was performed immediately

before or after the measurements to exclude

any lung pathologies.

Measurement

All patients were ventilated with a ServoI

Ventilator system (version 1.2, Siemens Medical

Group, Frankfurt, Germany). This was

necessary to use the monitoring capabilities of

Table 1. Clinically relevant data of patients in hemodynamically stable, controlled, mechanically ventilated conditions (reference group), patients in

nontraumatic, normothermic, witnessed cardiopulmonary arrest (cardiac arrest group), and patients during times of restoration of spontaneous circulation

(ROSC group)

Reference Group Cardiac Arrest Group ROSC Group

No 32 20 31

Age, yrs 50 (44–59) 55 (40–70) 54 (37–67)

Female, n (%) 9 (28) 6 (30) 7 (23)

BMI 25 (23–30) 29 (26–31) 28 (25–29)

Body temperature during measurements, °C 36.1 (33.5–36.8) [n _ 30] 35.1 (34.5–36.1) [n _ 11] 35 (34.5–35.7) [n _ 27]

Vasporessors used during measurements, n (%) 20 (63) 19 (95) 24 (77)

Vasodilatators used during measurements, n (%) 0 0 0

Cardiac rhythm during measurements, n (%)

Sinus 32 (100) 0 31 (100)

Ventricular fibrillation Not applicable 6 (30) Not applicable

Ventricular tachycardia 0 2 (10) 0 (0)

Asystole Not applicable 6 (30) Not applicable

Pulseless electrical activity Not applicable 13 (65) Not applicable

CPR duration, mins Not applicable 30 (2.25–70) Not applicable

Adrenaline used during resuscitation before

measurements, mg

Not applicable 1.5 (0–6) 2 (0–6)

Admission diagnosis, n (%)

Cardiac arrest cardiac etiology 14 (44) 20 (100) 31 (100)

Cerebrovascular disease 9 (28) Not applicable 0

Intoxication 5 (16) Not applicable 0

Cardiogenic shock 2 (6) Not applicable 0

Sepsis (n, %) 1 (3) Not applicable 0

Gastrointestinal bleeding 1 (3) Not applicable 0

Patients history, n (%)

Mild pulmonary emphysema 1 (3) 1 (5) 2 (6)

Cardiomyopathy 4 (13) 1 (5) 3 (10)

Pulmonary artery embolism 1 (3) 3 (15) 3 (10)

Chest radiograph, n (%) 32 (100) 11 (55) 22 (71)

Pneumonia 4 (13) 0 2 (6)

Pneumothorax 1 (3) 0 0

Effusion 8 (25) 0 1 (3)

Edema 5 (16) 5 (25) 8 (26)

Enlarged cardiac silhouette 7 (22) 3 (15) 5 (16)

Atelectasis 3 (9) 1 (5) 1 (3)

Pacemaker 3 (9) 2 (10) 2 (6)

ROSC, restoration of spontaneous circulation; BMI, body mass index; CPR, cardiopulmonary resuscitation.

Data are presented as the n (%) or as median (interquartile range; range from the 25th to the 75th percentile).

2 Crit Care Med 2006 Vol. 34, No. 9

the ServoI, which would not have been possible

under ongoing bag-valve-mask ventilation.

The ServoI was interfaced to a local server

(Vipdas Biosys GesmbH, Wien, Austria) for

continuous recording of ventilation data, such

as pressure flow and volume. This enabled the

recorded ventilator data to act as reference for

impedance data.

An investigational monitor/defibrillator

was used in the study to record thoracic impedance

(Heartstart 4000SP, Laerdal Medical

Cooperation, Stavanger, Norway). This device

was equipped with additional investigational

capabilities of recording thoracic impedance

changes related to ventilation. Heartstart

4000SP with the necessary analysis software

was provided by Laerdal Medical. The thorax

impedance measurements were recorded using

commercially available self-adhesive electrode

defibrillator pads (Heartstart Pads, Philips

Medical Systems, Seattle, WA). Male patients’

chest were not shaved, and no additional adherence

pressure was applied to the pads.

Reference Group

The patients in the reference group were

ventilated with tidal volumes of 400, 600, 800,

and 1000 mL each for 2 mins, and the resulting

impedance changes were recorded via defibrillator

pads in recommended standard positions

with the left apical pad “to the left of the nipple

with the center of the electrode in the midaxillary

line” and correlated with tidal volumes

given by the mechanical ventilation device.

To evaluate the impact of alternative pad

displacement on the measurement of tidal volume

via thoracic impedance change (17–19),

the left apical electrode was relocated three

times. For pad position B, the left apical pad

was placed far down with the lower end at the

crista illiaca. For pad position C, the left apical

pad was placed beneath the sternal electrode

on the left side of the sternum. Pad position D

was the same as position A, with the left apical

pad rotated 90°. The right sternal electrode

remained in standard position. For each position,

the patients were ventilated with a tidal

volume of 600 mL for 2 mins.

Cardiac Arrest and ROSC

Groups

To investigate whether cardiac arrest caused

variations in the impedance response, we elected

to record data from patients in and after cardiac

arrest. Ventilations were performed in accordance

with standard CPR procedures, with the

pad in the standard position A. Measurements

include periods of cardiac arrest (no pulse or

blood flow detected) (cardiac arrest group) and

monitoring periods after return of spontaneous

circulation (ROSC group). Because of artifacts

during ongoing external chest compressions,

only ventilation segments without chest compressions

were used for analysis.

Data Analysis

The tidal volume and impedance data were

analyzed with Matlab 7.0 (The MathWorks,

Figure 1. A, sample volume trace and resulting thorax impedance signal for a patient weighing 120 kg and ventilated with a tidal volume of 600 mL. B, the same

traces after noise reduction with filtering. C, the volume measurement in A is then plotted against the impedance trace to show the correlation C. The linearity

of the relationship is even more evident in D, which shows the volume measurements in B plotted against the resulting impedance change.

Crit Care Med 2006 Vol. 34, No. 9 3

Natick, MA). A change in lung volume, denoted

_V, will cause a transthoracic impedance

change, denoted _Z. According to Baker

et al. (20 –22), the relationship between impedance

change and lung volume for an individual

is essentially linear (_Z _ aDV). The

parameter _ is termed the impedance coefficient.

By dividing lung volume by the weight

W of the patient, the specific lung volume,

expressed in mL/kg, is obtained. The relationship

between impedance change _Z and specific

lung volume can be expressed as _Z _

_w(_V/W). The parameter _w _ A • W will in

this work be termed the specific impedance

coefficient. _ and _w are expected to vary from

individual to individual.

To explore the potential of using thorax

impedance for measuring ventilation rate and

inspiration time, we investigated the correlation

of waveforms between the lung volume

_V and the impedance waveform _Z. We also

explored the improvement in correlation

when removing pulse artifacts (12) and baseline

drift in the impedance channel with a

finite impulse response equiripple band-pass

filter. The filter was used on both the impedance

and the volume measurements to impose

the same effects on both signals. The correlation

between the impedance curve-forms was

analyzed in terms of linearity by performing a

robust linear regression (23) to each ventilation

measurement pair (_V, _Z) to model

their relationship. The constant term of the

model was forced to zero so that for zero

impedance change we estimate a tidal volume

of zero. The maximum deviation in volume

from the linear model, here termed the maximum

prediction error, was then calculated

for each ventilation measurement pair and

averaged across all ventilations. The correlation

coefficient (24) between each measurement

pair was also calculated. Average correlation

coefficients were calculated for each

patient and pad position, before and after filtering.

A high similarity in waveform implies

good potential for using impedance for quantifying

ventilation rate and inspiration time.

To investigate whether thorax impedance

can also be used for tidal volume estimation,

we measured the impedance change _ZT from

onset of inspiration to onset of expiration for

all compression-less ventilations with a distinct

tidal volume _VT (mL). Based on the

measurements of _ZT and _VT and the measured

weight W of the patient, the average

coefficients _ and _w for each patient in all

groups were estimated as the average impedance

change divided by the (specific) tidal volume

given. A specific tidal volume estimate

_Vest of an observed _ZT can then be found as

_ZT /aw, which can be considered as a tidal

volume estimation model.

We evaluate the impedance as a source for

tidal volume estimation by finding the model

estimation error. We first evaluate the patientspecific

model for each patient and then use

the average of _w over all patients with defibrillator

pads in standard position as a general

model. The general model is then evaluated

over the entire patient material. Finally we

calculate the estimation error of the general

model when the pads are in different positions

(25).

RESULTS

Characteristics of Study

Subjects

In the reference group, 32 of 37 patients

in hemodynamically stable, controlled,

mechanically ventilated conditions

could be used for analysis. Due to

data transfer problems between the monitor

and our computer-based data analysis

system, the remaining five patients

had to be excluded. For 26 patients, measurements

were available for all pad positions

A–D. The remaining six patients

were only measured in pad position A.

Admission diagnosis, known medical history,

and other relevant clinical data are

shown in Table 1.

In the group of patients in or after cardiac

arrest, 101 patients were eligible for

entry into the study. For further analysis,

41 patients’ data were available, because in

60 patients simultaneous ventilation recordings

were not available due to having

patients ventilated via a bag valve system

and not the ventilator. Under cardiac arrest

(pulseless conditions), 20 of these patients

could be analyzed (cardiac arrest group).

Those patients either were admitted under

ongoing chest compressions by the ambulance

service (n _ 12) or had a witnessed

cardiac arrest in our department (n _ 8);

Figure 2. Mean thorax impedance change for each patient at tidal volumes of 400, 600, 800, and 1000

mL, with the tidal volumes expressed in mL (A) and mL/kg (. Each patient is represented with one

set of markers for each tidal volume.

4 Crit Care Med 2006 Vol. 34, No. 9

six of the latter patients rearrested after

achieving restoration of spontaneous circulation

out of hospital. Spontaneous circulation

was restored in 31 patients (nine of

the former cardiac arrest group) during the

resuscitation attempt (ROSC group). Patient

characteristics, reasons for admittance,

and clinically relevant data for cardiac

arrest and ROSC patients are shown in

table 1.

Main Results

Correlation Between Volume and Impedance

Waveforms. Figure 1 shows a

volume trace from a patient in the reference

group and the corresponding thorax

impedance signal before and after filtering.

In Figure 1C and 1D, the volume trace is

plotted against the resulting impedance.

The mean (SD) correlation between the tidal

volume waveforms and impedance waveforms

for all ventilation cycles of all reference

group patients in pad position A was

calculated to be .971 (.027) before filtering

and .9996 (.0008) after filtering. The correlations

in the other pad positions were similar.

For the ROSC group, the correlation

was .969 (.032) and .9996 (.0009) before

and after filtering. For the cardiac arrest

group, the correlation was .967 (.035) before

filtering.

Relationship Between Tidal Volume

and Impedance Change. Figure 2A shows

the measured thorax impedance change for

tidal volumes of 400, 600, 800, and 1000

mL for all patients in the reference group

for pad position A. Figure 2B shows the

same data as a function of specific tidal

volume in mL/kg. It is seen that the measurement

points for each patient essentially

fall on a straight line, confirming a linear

relationship across the entire tidal volume

range.

The mean (SD) of the impedance coefficients

_ and _w for all useable patients in

the reference group in pad position A were

.00195 (.00066) _/mL and .148 (.035)

_/kg/mL. It is seen that the percent-wise SD

for the specific impedance coefficient _w

(24%) is lower than for the impedance coefficient

_ (34%), which implies that the

impedance is more accurate for estimating

the specific tidal volume. For all patients in

all groups, the mean (SD) of the impedance

coefficients _ and _w was .00194 (.0078)

_/mL and .152 (.048) _/kg/mL.

Accuracy of Tidal Volume Estimation.

Figure 3 shows the estimation error of

using the impedance for estimation of

tidal volume. In Figure 3A a patientspecific

model is used, and in Figure 3B a

general model calculated from the entire

data material is used. For the patientspecific

model, most errors fall within 1

mL/kg of the true tidal volume. The mean

(SD) estimation error for each patient is .0

(.108) for the patient-dependent model,

with an SD of .0 for the patient means. If

assuming that the estimation error is

normal distribution, this implies that an

estimate of 10 mL/kg will have an estimation

error _2 mL/kg 95% of the time.

The general model is less accurate, with a

Figure 3. Estimation error overview of (A) the patient-fitted model and ( the general model. Each

bin represents the percentage of ventilations with a specific estimation error for a specific tidal volume.

The size of one bin is 0.5 _ 0.5 mL/kg.

Crit Care Med 2006 Vol. 34, No. 9 5

larger spread in the estimation errors.

For this model, the mean (SD) estimation

error for each patient is .0 (.103), which

is similar to the patient-dependent

model. The SD of the patient means is,

however, .365. If we assume that the patient

means are normally distributed, this

implies that for _30% of the patients, the

mean estimation error will be _36.5% of

the true tidal volume.

Effect of Pad Position. Figure 4 shows

box plots of the mean estimation error for

each patient using the general model described

previously. We observed that the

spread of the estimation error is the same

in the different pad positions. In pad positions

B and C, the tidal volume is more

susceptible to overestimation.

DISCUSSION

Choosing appropriate impedance

thresholds for detecting the start and

stop point of each ventilation enables to

us estimate inspiration time and ventilation

rate with good accuracy as a new

concept in a clinical situation of advanced

cardiac life support after cardiac arrest.

As indicated by Figures 1 and 2, there is a

very good correlation between tidal volume

and impedance waveform.

Although several studies prove the importance

of correct pad placement for defibrillation

or cardioversion, in daily routine

most of the defibrillator pads are not placed

according to guidelines (5, 17, 18). We

found that the high correlation between

impedance and tidal volume waveforms is

not affected by alternative placement of the

pads. This shows the robustness of the

method for ventilation rate and inspiration

time monitoring. The spread in _w across

the patient group is found to be lowest for

pad position A. This is an advantage, since A

is the recommended position for the defibrillator

pads and the normal position in a

cardiac arrest situation. The specific impedance

coefficient is generally lower for pad

positions B, resulting in an underestimation

of the tidal volume for these positions.

By means of signal filtering, pulse and

chest compression artifacts and noise can

be removed and the correlation further improved,

thus making monitoring necessary

not only during isolated rescue breathing

but also during segments of chest compressions.

The filter employed in this work is an

offline filter, which will introduce a significant

signal delay, in the order of seconds.

For electrocardiographic signals, chest

compression artifacts have been successfully

removed by advanced filtering techniques

(26). To investigate the use of similar

techniques to remove artifacts from

impedance signals is, however, beyond the

scope of this article. Therefore, no measurements

have been carried out during

ongoing chest compressions.

For quantifying tidal volume, the large

variation in the measured impedance coefficients

represents a challenge. The physical

mechanisms contributing to the interpatient

variation in the impedance

coefficient _ are not fully understood, but

weight is an influencing factor. By dividing

tidal volume with patient weight to obtain

the specific impedance coefficient _w, the

variation is reduced. This is in accordance

with results from Valentenuzzi et al. (22),

who found that there is an inverse correlation

between the impedance coefficient and

body weight. Baker and Geddes (21) observed

that the impedance coefficient was

correlated with the type of body build.

However, we found no correlation between

_w and the body mass index of the subjects.

Trying to group our patient material based

on visual appearance did not provide further

insight on the inter-patient variation.

It therefore seems questionable whether

impedance-based feedback on ventilation

volume will have any advantage over observing

chest rise (7).

Limitations of our study are that no

measurements were carried out using a

bag-valve-mask, which is a more widespread

technique than using a ventilator.

However, since thoracic impedance is first

of all affected by changes in the lung volume,

it is reasonable to assume that a high

correlation would be found also with the

use of a bag-valve-mask.

Despite these potential drawbacks,

many investigators (11, 27–34) have reported

that transthoracic impedance plethysmography

correlates well with reference

standard clinical measurement of respiratory

rate.

If clinical measurement of respiratory

rate and volume is inaccurate or impractical,

an obvious imperative is to seek an

alternative. There is a long list of proposed

alternatives (35). All of them have been

reported to correlate well with “criterion

standard” clinical measurement of respiratory

rate. We chose to use transthoracic

impedance plethysmography in this study

because it could easily be used via AED pads

and its use has not been described in a

life-threatening situation such as advanced

cardiac life support after cardiac arrest.

The potential for a study bias needs to be

addressed as a result of the number of exclusions

necessary by the technical potentialities

and by the comorbidity of our patients.

Our study does not encompass

patients with COPD or ventilations during

gasping, which may limit the generalizability

of our findings.

Rescuers who encounter an unconscious

patient are trained to follow the

chain of survival developed by the American

Heart Association (5). Checking for

signs of circulation and breathing is fundamental.

Optimally, rescuers would be appropriately

directed to perform initial defibrillation

and chest compression in

settings of primary cardiac arrest and to

provide initial attention to the airway and

ventilation in instances of asphyxial cardiac

arrest. However, there is presently no capability

on the part of lay rescuers to distinguish

between primary cardiac arrest and

asphyxial arrest. Impedance is measured

Figure 4. Distribution (box plot) of the mean relative estimation error per mL/kg of tidal volume given

for the general model at different pad positions.

6 Crit Care Med 2006 Vol. 34, No. 9

through the defibrillator pads in their standard

position. If incorporated into an AED,

this technique can thus be used to monitor

ventilation rate and inspiration time in a

cardiac arrest situation, as an aid to give

ventilation-related feedback to the rescuer.

There is increasing evidence that feedback

during CPR is important because of the bad

quality of CPR (1–4). CPR quality could be

improved by monitoring ventilation activity

and giving real-time feedback to avoid

hyperventilation or inadequate ventilation

(9, 13). This monitoring/feedback technique

was designed to be incorporated into

conventional AEDs and to work in conjunction

with the information derived from

rhythm analyses by the AED. The equipment

is familiar to medical personnel and

is user friendly. Impedance plethysmography

was described as early as 1897 by Stewart

and proposed for noninvasive measurements

of cardiac output (33, 34, 36–38).

Further studies have to prove whether

the method is valid if only bag-valve-mask

ventilation is employed, whether esophageal

intubations could be detected, and

whether the device could also be used in

pediatric patients, after traumatic injuries,

during drowning, after obstruction to the

airway by food or other particulates, or in

settings of sudden infant death.

CONCLUSION

The present study showed that the impedance

measurement system sensor of a

defibrillator is likely to provide adequate

monitoring of the presence or absence of

ventilations, which would also allow

quantification of ventilation rates and inspiration

times. However, this technology,

at its present state, provides only limited

practical means for exact tidal volume

estimation.

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