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American Journal of Critical Care. 2007;16: 520-518
Copyright © 2007 by the American Association of Critical-Care Nurses.
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Cases of Note features peer-reviewed case reports and case series that document clinically relevant findings from critical and high acuity care environments. Cases that illuminate clinical diagnoses and management issues in the treatment of critically and acutely ill patients and include discussion of the patient’s experience with the illness or intervention are encouraged. Proposals for future Cases of Note articles may be e-mailed to ajcc{at}aacn.org.

Hyperinsulinemic Euglycemia Therapy for Verapamil Poisoning: Case Report

By Nirav P. Patel, MD, Meredith E. Pugh, MD, Steven Goldberg, MD and Glenn Eiger, MD. Nirav P. Patel is a fellow in the Division of Pulmonary, Allergy, and Critical Care Medicine and the Center for Sleep and Respiratory Neurobiology, and Meredith E. Pugh is chief resident in the Department of Medicine, at the Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. Steven Goldberg, director of the medical intensive care unit, and Glenn Eiger, associate chairman for the department of medicine, are both members of the Division of Pulmonary and Critical Care Medicine, Albert Einstein Medical Center, in Philadelphia.

Corresponding author: Nirav P. Patel, MD, Center for Sleep and Respiratory Neurobiology, Division of Pulmonary, Allergy, and Critical Care Medicine, 3600 Spruce St, 973 Maloney Bldg, Hospital of the University of Pennsylvania, Philadelphia, PA 19104 (e-mail: nirav.patel{at}uphs.upenn.edu).


   Abstract
Top
 Abstract
Case Report
 Discussion
 References
 
A 49-year-old woman was brought to the emergency department because of an intentional overdose of sustained-release verapamil along with captopril and glyburide. The estimated interval between ingestion and the time she was found was several hours. Initial findings were blood pressure 72/39 mm Hg, heart rate 32/min, and a score of 9 on the Glasgow Coma Scale. She was intubated and given intravenous fluid and vasopressor support. Decontamination with activated charcoal was instituted. Administration of dopamine and norepinephrine, atropine, sodium bicarbonate, and calcium chloride did not yield significant clinical improvement. Hyperinsulinemic euglycemia therapy was started: a bolus of regular insulin then infusions of insulin and 10% dextrose. After 24 hours of therapy, the bradycardia resolved and the patient’s hemodynamic condition stabilized with normalization of cardiac indices. On day 5 the patient was transferred to the medical unit, and on day 8 she was discharged to psychiatric care.

Verapamil is a potent calcium channel blocker (CCB) used to treat a variety of common cardiovascular abnormalities, including hypertension, angina pectoris, and supraventricular arrhythmias. Often verapamil is implicated in intentional and unintentional drug overdoses. According to the Toxic Exposure Surveillance System of the American Association of Poison Control Centers,1 10513 CCB overdoses were reported in 2004; 62 resulted in death. Furthermore, in 2004, an additional 356 cases with major toxic effects due to verapamil, defined as a permanent or life-threatening adverse clinical event, and 5202 cases of verapamil overdose requiring treatment at a healthcare facility were reported.1 Verapamil overdose is a costly problem that can lead to devastating outcomes. Treatment of such cases is a challenge.

Hyperinsulinemic euglycemia (HIE) therapy is a novel approach to treatment of CCB overdose. Insulin infusions, often with concomitant administration of glucose to prevent hypoglycemia, are used to treat life-threatening CCB overdose. Despite the emergence of a distinct clinical description of CCB poisoning, the optimal treatment remains unclear. We report the clinical course of a case of intentional severe verapamil overdose. (For a review2 of HIE therapy in verapamil poisoning, see pages 498–503.)


   Case Report
Top
 Abstract
 Case Report
Discussion
 References
 
A 49-year-old woman with no known medical history was brought to the emergency department because of an intentional overdose of sustained-release verapamil (5.8 g) along with captopril (1.5 g) and glyburide (65 mg). The patient was found "cold" by her husband and was transported to the emergency department immediately. The interval between ingestion and the time she was found was unknown, but it was estimated to be several hours.


Verapamil can cause major toxic effects, with more than 5000 cases per year requiring treatment.

 

On evaluation, the patient had a blood pressure of 72/39 mm Hg and a heart rate of 32/min. Her score on the Glasgow Coma Scale was 9. Her condition rapidly deteriorated, necessitating endotracheal intubation for airway protection and the institution of intravenous fluid and vasopressor support with dopamine and norepinephrine. Activated charcoal was administered via a nasogastric tube, although it was recognized that this treatment might have been too late to be beneficial because the time of ingestion of verapamil was not known.

The initial arterial blood gas analysis revealed a metabolic acidosis (pH of 7.16). Electrocardiograms showed an accelerated idioventricular rhythm at a rate of 50/min, and findings on a chest radiograph were unremarkable. Administration of dopamine at a rate of 18 µg/kg per minute and then norepinephrine at 35 µg/min did not cause any improvement in blood pressure. The patient subsequently received atropine, sodium bicarbonate, and a total of 13 ampules of calcium chloride (13 g) without significant clinical improvement. A transvenous pacer was inserted; however, electrical capture was inconsistent, and therefore the patient’s hemodynamic status remained stable.

Results of initial laboratory tests included potassium 5.8 mEq/L (5.8 mmol/L), serum urea nitrogen 33 mg/dL (11.8 mmol/L), creatinine 2.7 mg/dL (239 µmol/L), glucose 221 mg/dL (12.3 mmol/L), and hemoglobin 12.1 g/dL (121 g/L). Routine urine and serum toxicological screens did not reveal any additional ingestions.


Within 20 minutes of the start of HIE therapy, a sustained marked improvement in blood pressure and arterial pH occurred.

 

After consultation with the Philadelphia Poison Control Center, HIE therapy was started 90 minutes after the patient’s arrival in the emergency department. A bolus of regular insulin, 0.1 U/kg, was injected, then infusions of insulin, 0.25 U/kg per hour, and 10% dextrose were started. The goal was to administer 25 to 50 g of glucose per hour. Within 20 minutes, a sustained marked improvement in blood pressure and arterial pH occurred.

Thirty minutes later the patient was transferred to the medical intensive care unit. Her vital signs were more stable than before (blood pressure 82/64 mm Hg), and she had a paced rhythm with underlying intrinsic bradycardia of 36/min. Inspiratory crackles were auscultated in the lungs bilaterally, and the abdomen was moderately tender in the epigastric region. She was sedated; her pupils were 2 mm bilaterally and had a delayed response to light stimulus. Findings on a chest radiograph were consistent with pulmonary edema. A pulmonary artery catheter was placed, and hemodynamic monitoring revealed a cardiac output of 3.8 L/min and a pulmonary capillary wedge pressure of 14 to 16 mm Hg.

HIE therapy was continued for 24 hours. During this time the bradycardia resolved, obviating cardiac pacing, and her hemodynamic condition stabilized with normalization of cardiac indices. She still needed dopamine (1–3 µg/kg per minute) for blood pressure support. Concomitant sulfonylurea overdose resulted in recurrent episodes of hypoglycemia that were treated with dextrose infusions; the patient had no recognizable complications due to hypoglycemia. Other complications that ensued in the first 48 hours included intermittent pyrexia, acute pancreatitis, and worsening renal function (serum creatinine 5.2 mg/dL [459.7 µmol/L]). By day 4, the patient was more responsive, with a score of 14 on the Glasgow Coma Scale, and she was weaned off dopamine. Electrocardiograms revealed sinus rhythm, and the serum creatinine level showed marked improvement and eventually normalized. On day 5 the patient was transferred to the medical unit, and on day 8 she was discharged to psychiatric care.


Serum levels of verapamil are not uniformly predictive of outcome.

 


   Discussion
Top
 Abstract
 Case Report
 Discussion
References
 
In this severe case of verapamil overdose, the hallmark cardiac toxic effects were apparent when the patient was brought to the emergency department. Traditional decontamination and supportive measures did not stabilize her rapidly deteriorating condition. Furthermore, repeated doses of intravenous calcium chloride, sodium bicarbonate, and atropine sulfate did not markedly improve hemodynamic parameters and arterial pH. HIE therapy appears to have had a positive effect on initial stabilization and on the patient’s eventual outcome. In our review article2 in this issue, we discuss the current literature on HIE therapy and describe other available therapies for CCB intoxication.

CCB overdose can result in devastating cardiovascular compromise, emphasizing the importance of calcium’s effects in myocardial and endothelial cells. Although most of the reported cases3–10 of CCB overdose did not result in death, in a significant number the patients had critical illness and life-threatening sequelae. CCB overdoses are a challenge for clinicians. Verapamil is the drug most often implicated in fatal CCB overdoses,1 although the concentration needed for a fatal overdose is variable. Deaths have occurred with low verapamil concentrations (as low as 590 ng/mL), and survival has been reported in patients with serum concentrations of 4000 ng/mL.11 Therefore, serum levels of verapamil are not uniformly predictive of outcome.12

FINANCIAL DISCLOSURES
None reported.

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   REFERENCES
Top
 Abstract
 Case Report
 Discussion
 References
 

  1. Watson WA, Litovitz TL, Rodgers GC Jr, et al. 2004 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. 2005;23(5):589–666.[Medline]
  2. Patel NP, Pugh ME, Goldberg S, Eiger G. Hyperinsulinemic euglycemia therapy for verapamil poisoning: a review. Am J Crit Care. 2007;16:000–000.
  3. Yuan TH, Kerns WP, Tomaszewski CA, Ford MD, Kline JA. Insulin-glucose as adjunctive therapy for severe calcium channel antagonist poisoning. JToxicol ClinToxicol. 1999;37:463–474.
  4. Morris-Kukoski CL, Biswas AK, Parra M, Smith C. Insulin "euglycemia" therapy for accidental nifedipine overdose [abstract]. JToxicol ClinToxicol. 2000;38:577.
  5. Boyer EW, Shannon M. Treatment of calcium channel blocker intoxication with insulin infusion [letter]. N Engl J Med. 2001;344:1721–1722.[Free Full Text]
  6. Herbert J, O’Malley C, Tracey J, Dwyer R, Power M. Verapamil overdosage unresponsive to dextrose/insulin therapy [abstract]. JToxicol ClinToxicol. 2001;39:293–294.
  7. Rasmussen L, Husted SE, Johnsen SP. Severe intoxication after an intentional overdose of amlodipine. Acta Anaesthesiol Scand. 2003;24:1038–1040.
  8. Place R, Carlson A, Leiken J, Hanashiro P. Hyperinsulin therapy in the treatment of verapamil overdose [abstract]. JToxicol ClinToxicol. 2000;38:576–577.
  9. Marques M, Gomes E, de Oliveira J. Treatment of calcium channel blocker intoxication with insulin infusion: case report and literature review. Resuscitation. 2003;57:211–213.[Medline]
  10. Meyer MT, Stremski E, Scanlon MC. Successful resuscitation of a verapamil intoxicated child with a dextrose-insulin infusion. Clin Intensive Care. 2003;14(3–4):109–113.
  11. Krenzelok EP. Acute calcium channel blocker overdosage. ClinToxicol Forum. 1991;3:1–6.
  12. Chan LFT, Chhuy LH, Crowley RJ. Verapamil tissue concentration in fatal cases. J Anal Toxicol. 1987;11(5):171–174.[Medline]

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Hyperinsulinemic Euglycemia Therapy for Verapamil Poisoning: A Review
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N. P. Patel, M. E. Pugh, S. Goldberg, and G. Eiger
Hyperinsulinemic Euglycemia Therapy for Verapamil Poisoning: A Review
Am. J. Crit. Care., September 1, 2007; 16(5): 498 - 503.
[Abstract] [Full Text] [PDF]

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