Use of Vasopressin

[Ace844]

(Journal of Emergency Medicine

Volume 31 @ Issue 1 , July 2006, Pages 65-68

doi:10.1016/j.jemermed.2005.08.012

Copyright © 2006 Elsevier Inc. All rights reserved.

Selected topic: Toxicology

Vasopressin treatment for cyclic antidepressant overdose

James David Barry MD⁎, , David W. Durkovich DO† and Saralyn R. Williams MD‡

†Department of Emergency Medicine, Naval Medical Center, San Diego (NMCSD), San Diego, California

‡Department of Emergency Medicine, University of California, San Diego (UCSD), San Diego, California

⁎Department of Emergency Medicine, Brooke Army Medical Center, Fort Sam Houston, Texas

Received 1 June 2004; revised 14 April 2005; accepted 4 August 2005. Available online 22 June 2006)

Abstract

Due to neurotransmitter reuptake inhibition, peripheral alpha receptor blocking effects, and sodium channel blockade, severe cyclic antidepressant poisoning may lead to intractable hypotension. We report a case of severe amitriptyline toxicity, with hypotension unresponsive to direct alpha receptor agonists after pH manipulation, but improved with intravenous vasopressin. Vasopressin use in the setting of cyclic antidepressant toxicity has not been previously reported. Vasopressin may be a beneficial agent in the treatment of recalcitrant hypotension associated with poisoning or overdose. The anecdotal nature of this report must be emphasized and the use of vasopressin requires further research to define efficacy, dose, and potential side effects.

Introduction

Intractable hypotension may occur in the setting of many poisonings and overdoses. Direct acting alpha agonists may not consistently improve hypotension in the setting of severe poisonings. We report the beneficial use of intravenous (i.v.) vasopressin in a case of severe amitriptyline poisoning with hypotension unresponsive to direct α-receptor agonists and pH manipulation. To our knowledge, the use of vasopressin in the setting of cyclic antidepressant toxicity has not been previously reported. The mechanisms of vasopressin’s vasoconstrictive properties and its clinical uses are discussed.

Case report

A 56-year-old man was found unresponsive by paramedics, near an empty bottle of amitriptyline. Initial blood pressure was palpated at 80 mm Hg with a wide complex rhythm on the monitor. Therapy initiated by the paramedics included orotracheal intubation without sedation, one liter normal saline i.v. bolus, and 70 mEq sodium bicarbonate i.v. bolus. Enroute to the hospital the patient developed generalized tonic-clonic convulsions and received 5 mg of i.v. midazolam.

In the Emergency Department (ED), the vital signs were a pulse of 105 beats/min, blood pressure of 48/23 mm Hg, respiratory rate of 20 breaths/min with bag-valve ventilation, and temperature of 36.3°C (97.4°F). Pulse oximetry revealed a saturation of 97% on the 100% FIO2 via the bag-valve ventilation. Review of his past medical history revealed that he was positive for the human immunodeficiency virus (HIV) and he had a history of alcoholism. Other medications found in a separate room included clonazepam, vicodin, trazodone, and buproprion. Physical examination revealed no response to painful stimuli, recurrent episodes of seizure activity, and was remarkable for 3-mm pupils that were unresponsive to light. Corneal reflexes were absent. An electrocardiogram (EKG) demonstrated a junctional rhythm with QRS and QTc intervals of 156 and 552 ms, respectively, and a pronounced R wave in lead aVR. Resuscitation in the ED included a total of 3 L of normal saline, 400 mEq (8 ampules) of i.v. sodium bicarbonate, 10 mg lorazepam i.v., and a norepinephrine infusion. Multiple attempts at placement of a nasogastric tube were unsuccessful, so gastric decontamination was postponed.

Initial laboratory values revealed: sodium 143 mmol/L, potassium 3.6 mmol/L, chloride 108 mmol/L, bicarbonate 29 mmol/L, blood urea nitrogen 10 mg/dL, creatinine 1.2 mg/dL, glucose 76 mg/dL, aspartate aminotransferase 65 U/L, alkaline phosphatase 64 U/L, total bilirubin 0.4 mg/dL, creatinine phosphokinase103 U/L, magnesium 1.5 mg/dL, calcium 6.2 mg/dL, white blood cell count 4.9 K/cmm, hematocrit 36.8%, platelets 154 K/UL, plasma alcohol 125 mg/dL, salicylate < 1.0 mg/dL, acetaminophen 3.1 ug/mL. A urine immunoassay drug screen was positive for benzodiazepines as a class, opiates as a class, cyclic antidepressants as a class, and tetrahydrocannabinol.

In the intensive care unit (ICU), hypotension persisted despite titration of norepinephrine to 20 μg/min (Figure 1). The patient’s blood pressure improved only transiently during convulsive activity. Bicarbonate therapy (infusion and boluses) was continued, but further alkalinization was limited by a serum pH of 7.64. A lidocaine infusion titrated to 3 mg/min resulted in no change in clinical status. Because a nasogastric tube could not be placed while the patient was in the ED, an esophagogastroduodenoscopy (EGD) was performed and revealed a Billroth II anastomosis with erythema of the gastric remnant. Fifty grams of activated charcoal were administered during the EGD procedure, 4 ½ h after presentation.

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Figure 1. MAP vs. vasopressin.

Convulsions continued despite 48 mg of i.v. lorazepam and 5 mg of i.v. midazolam over 6 h. Severe persistent hypotension limited the administration of phenobarbital. A vasopressin infusion was started 5 h after arrival at 0.04 U/min and shortly thereafter i.v. phenobarbital was administered to control convulsions (total dose 2 g). The convulsions ceased and blood pressure improved over the next 3 h, allowing the norepinephrine infusion to be decreased. The initial hospital course was complicated by multiple episodes of wide complex tachycardia requiring cardioversion. Convulsions did not recur after phenobarbital loading and all vasopressor agents were weaned off by 35 h. The patient’s neurologic status gradually improved over the next 4 days. He was transferred from the ICU on hospital Day 5. He was discharged to the psychiatry service with no obvious neurologic sequelae on hospital Day 7.

Discussion

This case exemplifies the challenges in treating a severe cyclic antidepressant poisoning associated with wide complex dysrhythmias, recalcitrant hypotension, and persistent convulsions. In this patient, alkalemia (serum pH 7.64) limited further use of bicarbonate therapy. Hypertonic saline was considered, but not utilized because serum sodium was above 145 mEq/L after aggressive alkalinization. Lidocaine infusion failed to control dysrhythmias. Convulsions continued despite aggressive benzodiazepine therapy and barbiturate administration was limited by hypotension. Neuromuscular paralysis was considered, however, continuous electroencephalogram monitoring was not available. Hypotension was unresponsive to alkalinization, sodium loading, and high dose norepinephrine infusion. Glucagon was not considered. The etiology of the patient’s hypocalcemia was unclear, but serum alkalosis and ethanol ingestion are likely to have contributed. Vasopressin infusion was temporally related to an improvement in blood pressure and allowed completion of phenobarbital loading. In this way, the initiation of vasopressin coincided with the beginning of the patient’s stabilization.

Vasopressin (AVP) is an endogenous hormone released from the posterior pituitary when water deprivation or other factors lead to increased plasma osmolality, hypovolemia, or hypotension (1). Vasopressin receptors are widely distributed throughout the body and mediate the vascular and other non-renal actions of this hormone. Unlike V2 receptors that stimulate adenylate cyclase in the renal collecting duct system, V1 receptors work through a G-protein with actions strikingly similar to those of α1-adrenergic receptors. The binding of AVP to the V1 receptor leads to Gq-protein mediated activation of membrane-bound phospholipases (2). The activation of these phospholipases leads to a number of cellular events, resulting in increased intracellular calcium concentrations (1 and 3). In the smooth muscle cells of blood vessels, increased intracellular concentrations of calcium are the stimulus for vasoconstriction. In addition to stimulating vasoconstriction, AVP also inhibits vasodilatory mechanisms that contribute to hypotension and vascular hyporeactivity (2, 4, 5, 6 and 7).

Traditional inotropic agents and vasopressors (epinephrine, norepinephrine, dopamine, etc.) have diminished action in the setting of vasodilatory shock states (3, 4, 5, 6, 8, 9, 10, 11 and 12). Low-dose AVP infusions have resulted in significant increases in arterial blood pressure in these life-threatening hypotensive situations (2, 5, 6, 9, 11, 12 and 13). The dramatic response to AVP in these settings may be due to a relative AVP deficiency as suggested by documented low plasma concentrations (4, 6, 9, 11 and 14). Vasopressin also potentiates the vasoconstrictor effects of traditional inotropic agents such as norepinephrine (4, 5, 10 and 15).

Although AVP has gained praise in the critical care setting for the treatment of severe hypotension, there is little data regarding its use in the poisoned patient. Clinical studies utilizing vasopressin for intractable hypotension have been relatively small and focused only on physiologic end points (2, 5, 11, 12, 14, 16, 17 and 18). Extensive study of its efficacy, side effects, and dose response has not been performed. Although small studies have found no detrimental effects on end-organ perfusion and function (2, 5, 12, 13, 14, 16 and 17), AVP administration carries the theoretical risks of deleterious end-organ vasoconstriction (2, 4 and 18), decreased myocardial contractility (5, 10, 11 and 17), and microcirculatory occlusion by AVP-induced platelet aggregation (4 and 19). The most advantageous dose of AVP is unclear at this time. Although most authors advocate “low dose” AVP infusions, the definition of “low dose” is variable, ranging from 0.01U/min to 0.1U/min (10, 11, 15, 16, 17 and 18). Some have hinted that doses > 0.04U/min may be associated with increased adverse events (4 and 15).

Our case illustrates the use of vasopressin in the setting of severe intractable hypotension due to amitriptyline toxicity. Its use was temporally related to improvement in the patient’s blood pressure and may have played a role in the ultimate positive outcome in this case. Although amitriptyline poisoning was not confirmed with serum levels, the patient later admitted to an ingestion of an entire bottle of amitriptyline (actual number of pills unknown) and unknown quantities of alcohol in a suicide attempt. The history is consistent with the clinical course observed. Other vasoactive co-ingestants or medication effects (most notably propylene glycol from large doses of lorazepam administered) may have made less important contributions to his intractable hypotension. In addition to cyclic antidepressants, his urine drug screen was also positive for benzodiazepines and opiates consistent with his outpatient medications. Although the patient denied co-ingestants, ingestion of other medications or treatment medications could have contributed to the clinical presentation of intractable hypotension and convulsions. The institution of the vasopressin may have corresponded with the routine evolution of improvement seen in many patients with cyclic antidepressant poisoning.

Vasopressin is a novel vasopressor agent that may be beneficial in the treatment of intractable hypotension in the poisoning patient. The anecdotal nature of this report must be emphasized and the administration of vasopressin requires further investigation to determine efficacy, proper dose, and potential side effects.

References

1 E.K. Jackson, Vasopressin and other agents affecting the renal conservation of water. In: J.G. Hardman and L.E. Limbird, Editors, Goodman & Gillman’s the pharmacological basis of therapeutics (10th edn.), McGraw-Hill, New York (2000), pp. 789–808.

2 M.W. Dunser, J.A. Mayr and H. Ulmer et al., The effects of vasopressin on systemic hemodynamics in catecholamine-resistant septic and postcardiotomy shock a retrospective analysis, Anesth Analg 93 (2001), pp. 7–13. Abstract-MEDLINE

3 R.A. Hessler, Cardiovascular principles. In: L.R. Goldfrank, N.E. Flomenbaum, N.A. Lewin, M.A. Howland, R.S. Hoffman and L.S. Nelson, Editors, Goldfrank’s toxicologic emergencies (7th edn.), Appleton & Lange, Stamford, CT (2002), pp. 315–334.

4 C.L. Holmes, B.M. Patel and J.A. Russel et al., Physiology of vasopressin relevant to management of septic shock, Chest 120 (2001), pp. 989–1002. Abstract-Elsevier BIOBASE | Abstract-EMBASE | Abstract-MEDLINE | Full Text via CrossRef

5 D.L. Morales, D. Gregg and D.N. Helman et al., Arginine vasopressin in the treatment of 50 patients with postcardiotomy vasodilatory shock, Ann Thorac Surg 69 (2000), pp. 102–106. SummaryPlus | Full Text + Links | PDF (161 K)

6 D. Morales, J. Madigan and S. Cullinane, Reversal by vasopressin of intractable hypotension in the late phase of hemorrhagic shock, Circulation 100 (1999), pp. 226–229. Abstract-Elsevier BIOBASE | Abstract-EMBASE | Abstract-MEDLINE

7 D.W. Landry and J.A. Oliver, The pathogenesis of vasodilatory shock, N Engl J Med 345 (2001), pp. 588–595. Abstract-EMBASE | Abstract-Elsevier BIOBASE | Abstract-MEDLINE | Full Text via CrossRef

8 International Consensus on Science. Guidelines 2000 for cardiopulmonary resuscitation and emergency cardiovascular care, Circulation 102 (2000) (Suppl I), pp. I130–I131.

9 D.W. Landry, H.R. Levin and E.M. Gallant, Vasopressin deficiency contributes to the vasodilation of septic shock, Circulation 95 (1997), pp. 1122–1125. Abstract-MEDLINE

10 J.A. Gold, S. Cullinane and J. Chen et al., Vasopressin as an alternative to norepinephrine in the treatment of milrinone-induced hypotension, Crit Care Med 28 (2000), pp. 249–252. Abstract-EMBASE | Abstract-MEDLINE | Full Text via CrossRef

11 M. Argenziano, A.F. Choudhri and M.C. Oz, A prospective randomized trial of arginine vasopressin in the treatment of vasodilatory shock after left ventricular assist device placement, Circulation 96 (1997) (Suppl II), pp. II286–II290. Abstract-EMBASE

12 E.B. Rosenzweig, T.J. Starc and J.M. Chen et al., Intravenous arginine-vasopressin in children with vasodilatory shock after cardiac surgery, Circulation 100 (1999) (Suppl II), pp. II182–II186. Abstract-MEDLINE | Abstract-EMBASE | Abstract-Elsevier BIOBASE

13 M. Argenziano, J.M. Chen and S. Cullinane et al., Arginine vasopressin in the management of vasodilatory hypotension after cardiac transplantation, J Heart Lung Transplant 18 (1999), pp. 814–817. SummaryPlus | Full Text + Links | PDF (114 K)

14 J.M. Chen, S. Cullinane and T.B. Spanier et al., Vasopressin deficiency and pressor hypersensitivity in hemodynamically unstable organ donors, Circulation 100 (1999) (Suppl II), pp. II244–II246. Abstract-MEDLINE | Abstract-EMBASE | Abstract-Elsevier BIOBASE

15 C.L. Holmes, K.R. Walley and D.R. Chittock et al., The effects of vasopressin on hemodynamics and renal function in severe septic shock a case series, Intensive Care Med 27 (2001), pp. 1416–1421. Abstract-EMBASE | Abstract-MEDLINE | Full Text via CrossRef

16 B.M. Patel, D.R. Chittock and J.A. Russell et al., Beneficial effects of short-term vasopressin infusion during severe septic shock, Anesthesiology 96 (2002), pp. 576–582. Abstract-MEDLINE | Abstract-EMBASE | Full Text via CrossRef

17 J. Gold, S. Cullinane and J. Chen et al., Vasopressin in the treatment of milrinone-induced hypotension in severe heart failure, Am J Cardiol 85 (2000), pp. 506–508. SummaryPlus | Full Text + Links | PDF (86 K)

18 I. Tsuneyoshi, H. Yamada and K. Yasuyuki et al., Hemodynamic and metabolic effects of low-dose vasopressin infusions in vasodilatory septic shock, Crit Care Med 29 (2001), pp. 487–493. Abstract-MEDLINE | Abstract-EMBASE | Full Text via CrossRef

19 R.J. Gazmuri and S.A. Shakeri, Low dose vasopressin for reversing vasodilation during septic shock, Crit Care Med 29 (2001), pp. 673–675. Abstract-MEDLINE | Abstract-EMBASE | Full Text via CrossRef

[FL_Medic]

Wonder if you use Vasopressin much ?

Vassopressin is a great drug to get the pressor effects without all the other effects of Epi. I just think we need to get it pre packaged in a 40 unit sirynge. Time is tissue. Our new ACLS update also taught us that we will be using vasopressin in more algorythms.

[AZCEP]

Give it time and someone will have the revelation that they will sell more Vasopressin in a prefilled syringe than in vials.

The cardiac arrest algorithm is all inclusive now. You have a dead patient, they are all included on one algorithm. Basically, if the patient is pulseless, you can use vasopressin.

I for one would like to hear how well it works for you and your patients.

[FL_Medic]

Give it time and someone will have the revelation that they will sell more Vasopressin in a prefilled syringe than in vials.

The cardiac arrest algorithm is all inclusive now. You have a dead patient, they are all included on one algorithm. Basically, if the patient is pulseless, you can use vasopressin.

I for one would like to hear how well it works for you and your patients.

Well I don't really have a way to tell you how it works for my pt.'s simply because I have yet to only give vasopressin and get a pulse back. I have always given it with a disrythmic or/and other meds. I wish there was a way I could tell.

[Ace844]

Hello Everyone,

Here's a great albeit older paper which describes the MOA of Vasopressin.

HTH,

ACE844

[web:b6ac9a5814]http://arjournals.annualreviews.org/doi/pdf/10.1146/annurev.me.37.020186.000305[/web:b6ac9a5814]

[NCFD18]

Epi-shock, bicarb-shock? Uh........

bicarb? I hope that was a joke.

I think anyone in VT/VF would benefit more from an antidysrhythmic.