death of a sailor: an insulin overdose

1. Death of a Sailor: An Insulin Overdose LT Francesca Cimino, MD LT Mike Arnold, MD Naval Hospital Jacksonville Today I will be presenting an interesting but very tragic case of a young man who died because of his steroid and insulin abuse. I will highlight the difficulties we faced in diagnosing and treating him. I will underscore the importance of screening our active duty population for steroid use and other ergogenic supplement abuse. Today I will be presenting an interesting but very tragic case of a young man who died because of his steroid and insulin abuse. I will highlight the difficulties we faced in diagnosing and treating him. I will underscore the importance of screening our active duty population for steroid use and other ergogenic supplement abuse.

2. The 21yo AD seaman was brought to the ER after being found down in his barracks by his roommates, covered in vomit. He was diaphoretic and difficult to arouse. In the ER, he was found to be hypothermic, tachycardic, hypertensive and hypoxic. His initial accucheck was <20 The 21yo AD seaman was brought to the ER after being found down in his barracks by his roommates, covered in vomit. He was diaphoretic and difficult to arouse. In the ER, he was found to be hypothermic, tachycardic, hypertensive and hypoxic. His initial accucheck was <20

3. Past Medical History Known anabolic steroid user Treated for chronic hepatitis Recent MVA secondary to syncopal episode No history of diabetes or prescribed insulin His medical history was gathered through review of the AHLTA database. He been followed closely for complications related to steroid abuse, including chronic hepatitis, diagnosed by liver biopsy for elevated transaminases without an obvious cause. Although he denied current steroid use to his providers, he had recently told his case manager that he was still using a DHEA preparation. Just five days prior, he had been in an accident after becoming syncopal on the road. His BG during evaluation was 36. His medical history was gathered through review of the AHLTA database. He been followed closely for complications related to steroid abuse, including chronic hepatitis, diagnosed by liver biopsy for elevated transaminases without an obvious cause. Although he denied current steroid use to his providers, he had recently told his case manager that he was still using a DHEA preparation. Just five days prior, he had been in an accident after becoming syncopal on the road. His BG during evaluation was 36.

4. Pertinent physical findings Physical exam: Gynecomastia Testicular atrophy Initial ABG: 7.26/57/52/25/-2.4 Physical exam was significant for gynecomastia and testicular atrophy, which is c/w his previous clinical notes His initial ABG highlighted an uncompensated respiratory acidosis with significant hypoxia. Physical exam was significant for gynecomastia and testicular atrophy, which is c/w his previous clinical notes His initial ABG highlighted an uncompensated respiratory acidosis with significant hypoxia.

5. Pertinent labs Pertinent labs included hyperkalemia, an anion gap of 17, and elevated transaminases and CK. His metabolic acidosis, in combination with an elevated CK, may indicate that muscle breakdown was occurring at the time of presentation. Additionally, there was a mild elevation in the white count without left shift, or bands. His thrombocytosis was likely an acute phase reactant. Pertinent labs included hyperkalemia, an anion gap of 17, and elevated transaminases and CK. His metabolic acidosis, in combination with an elevated CK, may indicate that muscle breakdown was occurring at the time of presentation. Additionally, there was a mild elevation in the white count without left shift, or bands. His thrombocytosis was likely an acute phase reactant.

6. Initial Resuscitation 3 amps D50 2 L LR bolus CPAP Despite intervention: Glucose drops to 33 No improvement in ABG RSI with Etomidate and Succinylcholine ABG after intubation: 7.3/50/152/34/1.7 After 3 ampules of 50% dextrose the patient had minimal improvement in responsiveness. 2L LR were bolused for extreme tachycardia (130s) and h/h which showed hemoconcentration CPAP was initiated, due to his continuing tachypneic and respiratory acidosis, without significant improvement He became obtunded over the next 2 hours and required emergent intubation. Etomidate and succinylcholine were used for induction. After 3 ampules of 50% dextrose the patient had minimal improvement in responsiveness. 2L LR were bolused for extreme tachycardia (130s) and h/h which showed hemoconcentration CPAP was initiated, due to his continuing tachypneic and respiratory acidosis, without significant improvement He became obtunded over the next 2 hours and required emergent intubation. Etomidate and succinylcholine were used for induction.

7. ICU Course Tmax 105.4�F HR 140s-150s BP 170s-200s/50s-60s. Within 1 hour of his intubation, the patient�s temperature rose to 105.4. and remained elevated despite active cooling measures. He remained extremely tachycardic and hypertensive. Within 1 hour of his intubation, the patient�s temperature rose to 105.4. and remained elevated despite active cooling measures. He remained extremely tachycardic and hypertensive.

8. Differential Diagnosis Malignant hyperthermia Rhabdomyolysis Heat stroke Sepsis Drug reaction Central fever We stop here to consider the differential diagnosis of this hypermetabolic state. In our consideration was: malignant hyperthermia � secondary to rapid induction agents Rhabdo � as evidenced by his metabolic acidosis and his elevated CK Heat stroke � it is unkown if he had exercised prior to this event Sepsis � must be considered despite lack of left shift, hypotension, or source. Blood cultures eventually ruled this out Drugs � Cocaine/alcohol/PCP may present with similar findings. Central � unclear if he had suffered an anoxic event prior to EMS finding him.We stop here to consider the differential diagnosis of this hypermetabolic state. In our consideration was: malignant hyperthermia � secondary to rapid induction agents Rhabdo � as evidenced by his metabolic acidosis and his elevated CK Heat stroke � it is unkown if he had exercised prior to this event Sepsis � must be considered despite lack of left shift, hypotension, or source. Blood cultures eventually ruled this out Drugs � Cocaine/alcohol/PCP may present with similar findings. Central � unclear if he had suffered an anoxic event prior to EMS finding him.

9. Malignant Hyperthermia Hypermetabolic state caused by generalized muscle contractions Susceptible individuals have alteration in myocyte calcium channel Anesthetics prevent calcium channel from closing Tetanic contractions cause rhabdomyolysis His constellation of sx: CK elevation, progressive hyperkalemia, hyperthermia, and tachycardia associated with tetany and renal failure, especially in relation to induction with succinylcholine, lead us to consider MH as the diagnosis for immediate treatment. In MH � a receptor of myocyte�s calcium channel which controls calcium release from the SR, is already defective in susceptible patients. The trigger chemicals cause the channels to stick open, allowing a huge influx of calcium, creating tetany, heat and rhabdomyolysis. Temperatures in these patients can rise as quickly as 1 degree centrigrade every 5 minutes. His constellation of sx: CK elevation, progressive hyperkalemia, hyperthermia, and tachycardia associated with tetany and renal failure, especially in relation to induction with succinylcholine, lead us to consider MH as the diagnosis for immediate treatment. In MH � a receptor of myocyte�s calcium channel which controls calcium release from the SR, is already defective in susceptible patients. The trigger chemicals cause the channels to stick open, allowing a huge influx of calcium, creating tetany, heat and rhabdomyolysis. Temperatures in these patients can rise as quickly as 1 degree centrigrade every 5 minutes.

10. Final Course Dantrolene given Treated for hyperkalemia (7.8 mg/dl) with: Albuterol Insulin and glucose Lasix Kayexalate Calcium gluconate Cardiac arrest 9 hours after presentation The patient was given multiple doses of dantrolene, a drug that blocks the calcium influx, over the next 3 hours. He failed to improve. His potassium rose to 7.8. We attempted to treat his hyperkalemia with all methods possible, in order to transfer him to a facility with dialysis capability, but despite attempts to shift the potassium into the intracellular spaces, he suffered a fatal arrythmia and died less than 9 hours after his initial presentation. The patient was given multiple doses of dantrolene, a drug that blocks the calcium influx, over the next 3 hours. He failed to improve. His potassium rose to 7.8. We attempted to treat his hyperkalemia with all methods possible, in order to transfer him to a facility with dialysis capability, but despite attempts to shift the potassium into the intracellular spaces, he suffered a fatal arrythmia and died less than 9 hours after his initial presentation.

11. Autopsy Results Cause of death: Complications from chronic exogenous steroid use with acute exacerbation by exogenous insulin use. Multiple subcutaneous needle marks C-peptide 0.2 ng/ml Postmortem analysis revealed multiple SC marks on his abdomen, presumably from injecting insulin. His c-peptide of 0.2 ng/ml was markedly lower than tdhe normal of > 0.9, suggesting chronic exogenous ingestion of insulin. Postmortem analysis revealed multiple SC marks on his abdomen, presumably from injecting insulin. His c-peptide of 0.2 ng/ml was markedly lower than tdhe normal of > 0.9, suggesting chronic exogenous ingestion of insulin.

12. Steroids and Insulin Supplements used since inception of competition Over 50% of bodybuilders Insulin is an inexpensive adjunct to steroid use 25% of steroid users report insulin use Steroid use dates back to the 1930s, after the discovery of testosterone. Over the years, while big name athletes made headlines, the use of steroids and supplements have grown among the amateur sporting population. One study suggests that over 50% of current male body builders use steroids regularly. Insulin is a RELATIVE NEW COMER and a cheap adjunct to anabolic steroids in building muscle mass Easily accessible websites describe how to use insulin to improve workouts and add more muscle Insulin can be obtained for as little as $20 for 10 units OTC without a prescription In a small study of steroid users, 25% reported also using insulin as wellSteroid use dates back to the 1930s, after the discovery of testosterone. Over the years, while big name athletes made headlines, the use of steroids and supplements have grown among the amateur sporting population. One study suggests that over 50% of current male body builders use steroids regularly. Insulin is a RELATIVE NEW COMER and a cheap adjunct to anabolic steroids in building muscle mass Easily accessible websites describe how to use insulin to improve workouts and add more muscle Insulin can be obtained for as little as $20 for 10 units OTC without a prescription In a small study of steroid users, 25% reported also using insulin as well

13. Why Insulin? Recruits glucose transporters to cell membrane Increases amino acid transport into cells Should increase protein synthesis Amino acid transport only increased in hyperaminoacidemia in vitro Insulin recruits glucose transporters to the cell membrane but more importantly, it plays a role in amino acid transport into the cell, theoretically helping increase those building blocks of muscle protein, which is why some steroid uses �stack� their injections with insulin. In vitro research. however, suggests that effect doesn�t occur unless there is an enormous concentration of amino acids. Insulin recruits glucose transporters to the cell membrane but more importantly, it plays a role in amino acid transport into the cell, theoretically helping increase those building blocks of muscle protein, which is why some steroid uses �stack� their injections with insulin. In vitro research. however, suggests that effect doesn�t occur unless there is an enormous concentration of amino acids.

14. M-Cresol Preservative Used with: Succinylcholine Insulin In vitro studies demonstrate m-cresol produced tetanic contractions Insulin and Succinylcholine share an interesting link. They both contain the preservative, M CRESOL, which is thought to be the culprit in the malignant hyperthermia. Testing of the drug with the preservative in MH susceptible cells produced tetanic contractions while succinylcholine without the preservative did not. Since all COMERCIALLY AVAILABLE INSULIN HAS THE M-CRESOL PRESERVATIVE, it is likely that this young man�s insulin use may have contributed to his hypermetabolic state on admission.Insulin and Succinylcholine share an interesting link. They both contain the preservative, M CRESOL, which is thought to be the culprit in the malignant hyperthermia. Testing of the drug with the preservative in MH susceptible cells produced tetanic contractions while succinylcholine without the preservative did not. Since all COMERCIALLY AVAILABLE INSULIN HAS THE M-CRESOL PRESERVATIVE, it is likely that this young man�s insulin use may have contributed to his hypermetabolic state on admission.

15. Malignant Hyperthermia and Insulin Occurs during resuscitation from diabetic crises Described only in pediatric population A review of the literature revealed a link between malignant hyperthermia in relation to insulin in the pediatric population. MH-like syndrome has been described in kids who have suffered diabetic crises requiring large doses of insulin for resuscitation. These particular cases are ONLY in the pediatric literature Our research revealed no adult case of MH from insulin use in hyperglycemic crisis. A review of the literature revealed a link between malignant hyperthermia in relation to insulin in the pediatric population. MH-like syndrome has been described in kids who have suffered diabetic crises requiring large doses of insulin for resuscitation. These particular cases are ONLY in the pediatric literature Our research revealed no adult case of MH from insulin use in hyperglycemic crisis.

16. Summary Use of performance enhancing (anabolic) drugs is common. Insulin may trigger malignant hyperthermia and rhabdomyolysis. Insulin is cheap and readily available to our active duty population. While we will never know the exact cause of this sailor�s death, we can learn valuable lessons from this young man. First, use of anabolic agents is surprisingly common. We need to recognize insulin as ONE of those agents. Secondly, insulin may trigger rhabdomyolysis and even malignant hyperthermia in susceptible patients. Finally, insulin is cheap and easily accessible. Given the rarity of hypoglycemia in healthy individuals, it is important to suspect insulin abuse in our active duty population who present with hypoglycemic or syncopal events. When surveilling for supplement use, questioning should include the use of insulin. Thank you for your attention.While we will never know the exact cause of this sailor�s death, we can learn valuable lessons from this young man. First, use of anabolic agents is surprisingly common. We need to recognize insulin as ONE of those agents. Secondly, insulin may trigger rhabdomyolysis and even malignant hyperthermia in susceptible patients. Finally, insulin is cheap and easily accessible. Given the rarity of hypoglycemia in healthy individuals, it is important to suspect insulin abuse in our active duty population who present with hypoglycemic or syncopal events. When surveilling for supplement use, questioning should include the use of insulin. Thank you for your attention.