Sudden leg paralysis in a 26-year-old nurse

An analysis of overdose cases with g-hydroxybutyrate (GHB) and its precursor g-butyrolactone (GBL) reported to the Swiss Toxicological Information Centre was recently published by Liechti and Kupferschmid in this journal [1]. We want to add to the evolving clinical picture of GHB and GBL intoxications by reporting a recent case from our institution presenting with a hitherto unknown severe sequelae of GBL intake. Case report: A 26-year-old nurse woke up in the morning before Christmas and realized that she was unable to move and feel here legs. She crawled to the phone, called for help and was admitted to the emergency room. Upon arrival she was afebrile, fully orientated and conscious. Her past medical history was unremarkable and she repeatedly denied any substance abuse besides moderate cigarette smoking. Physical examination showed sensomotoric, painful paraparesis of both legs at the level L2–3 without clinical signs of meningitis. Both feet were cold with week arterial pulses. Toxic neuropathy, traumatic and neoplastic nerve compression, and GuillainBarré syndrome were considered. However, computed tomography of the lumbar spine and liquor samples were normal whereas laboratory tests revealed elevated muscle enzymes (creatine kinase 135’905 U/l, myoglobulin >30’000 U/l, lactate dehydrogenase 4’114 U/l, aspartate aminotransferase 1’877 U/l), creatinine (166 mmol/l), blood urea nitrogen (10.2 mmol/l), phosphate (2.2 mmol/l) and potassium (5 mmol/l), moderate anaemia (Hb10 g/dl) and neutrophilia (9.14 103/ml). Drug screening in the urine revealed the presence of cocain, benzodiazepine and cannabis, but no amphetamines or opiates. The medical history was reiterated and the patient disclosed having sniffed cocaine at a party four days earlier for the first time in her life. Despite vigorous volume replacement acute renal failure developed necessitating continuous hemodiafiltration and both legs exhibited progressive bluish discoloration. A clinical diagnosis of acute compartment syndrome was made. Elevated intracompartmental pressures (25–47 mm Hg, normal <10 mm Hg) were measured in both lower legs by the method of Stryker [2] and immediate surgical fasciotomia and decompression was performed. Thereafter, the patient’s condition improved within a week, the muscle compartments were closed and hemodiafiltration was stopped. Upon repeated compassionate history taking the patient reported occasional intake of GHB and a massive intake of GBL with a suicidal intention on the evening before admission. Mimicking sensomotoric palsy, this patient suffered from severe rhabdomyolysis leading to acute renal failure and compartment syndrome after GBL use. Since GBL induces rapid coma that only lasts a few hours [3] it is likely that the combination of sedative substances was responsible for a prolonged unconsciousness and immobility leading to muscle compression and damage. Alternatively, GBL might have direct myotoxic effects possibly in combination with cocaine. In this regard it is noteworthy that GHB is used as muscle building agent and that Liechti and Kupferschmid described elevated creatine kinase levels [1]. The short half-life restricts detection of GHB/GBL by gas or liquid chromatography-mass spectrometry in serum or urine samples to 6–12 hours after intake [4, 5], which was not feasible in the present case. In summary, rhabdomyolysis is a rare but well recognized complication of methylenedioxymethamphetamine (MDMA; “Ecstasy”) and cocaine abuse [6, 7] but it has not yet been recognised as a potential lethal sequelae of GHB/GBL intoxication.

An analysis of overdose cases with g-hydroxybutyrate (GHB) and its precursor g-butyrolactone (GBL) reported to the Swiss Toxicological Information Centre was recently published by Liechti and Kupferschmid in this journal [1].We want to add to the evolving clinical picture of GHB and GBL intoxications by reporting a recent case from our institution presenting with a hitherto unknown severe sequelae of GBL intake.
Case report: A 26-year-old nurse woke up in the morning before Christmas and realized that she was unable to move and feel here legs.She crawled to the phone, called for help and was admitted to the emergency room.Upon arrival she was afebrile, fully orientated and conscious.Her past medical history was unremarkable and she repeatedly denied any substance abuse besides moderate cigarette smoking.Physical examination showed sensomotoric, painful paraparesis of both legs at the level L2-3 without clinical signs of meningitis.Both feet were cold with week arterial pulses.Toxic neuropathy, traumatic and neoplastic nerve compression, and Guillain-Barré syndrome were considered.However, computed tomography of the lumbar spine and liquor samples were normal whereas laboratory tests revealed elevated muscle enzymes (creatine kinase 135'905 U/l, myoglobulin >30'000 U/l, lactate dehydrogenase 4'114 U/l, aspartate aminotransferase 1'877 U/l), creatinine (166 mmol/l), blood urea nitrogen (10.2 mmol/l), phosphate (2.2 mmol/l) and potassium (5 mmol/l), moderate anaemia (Hb10 g/dl) and neutrophilia (9.14 ҂ 10 3 /ml).Drug screening in the urine revealed the presence of cocain, benzodiazepine and cannabis, but no amphetamines or opiates.The medical history was reiterated and the patient disclosed having sniffed cocaine at a party four days earlier for the first time in her life.Despite vigorous volume replacement acute renal failure developed necessitating continuous hemodiafiltration and both legs exhibited progressive bluish discoloration.A clinical diagnosis of acute compartment syndrome was made.Elevated intracompartmental pressures (25-47 mm Hg, normal <10 mm Hg) were measured in both lower legs by the method of Stryker [2] and immediate surgical fasciotomia and decompression was performed.Thereafter, the patient's condition improved within a week, the muscle compartments were closed and hemodiafiltration was stopped.Upon repeated compassionate his-tory taking the patient reported occasional intake of GHB and a massive intake of GBL with a suicidal intention on the evening before admission.
Mimicking sensomotoric palsy, this patient suffered from severe rhabdomyolysis leading to acute renal failure and compartment syndrome after GBL use.Since GBL induces rapid coma that only lasts a few hours [3] it is likely that the combination of sedative substances was responsible for a prolonged unconsciousness and immobility leading to muscle compression and damage.Alternatively, GBL might have direct myotoxic effects possibly in combination with cocaine.In this regard it is noteworthy that GHB is used as muscle building agent and that Liechti and Kupferschmid described elevated creatine kinase levels [1].The short half-life restricts detection of GHB/GBL by gas or liquid chromatography-mass spectrometry in serum or urine samples to 6-12 hours after intake [4,5], which was not feasible in the present case.In summary, rhabdomyolysis is a rare but well recognized complication of methylenedioxymethamphetamine (MDMA; "Ecstasy") and cocaine abuse [6,7]  The most common causes of rhabdomyolysis (creatine kinase (CK) level >1000 U/l) in emergency department (ED) patients are drugs of abuse, exercise, and immobilization [1].Drugs of abuse associated with rhabdomyolysis include cocaine, heroin, ethanol, amphetamines, barbiturates, phencyclidine, and others [2].The most frequent single cause of rhabdomyolysis in a series of ED patients was cocaine use [1].Additional risk factors or causes for rhabdomyolysis and associated renal failure are agitation, hyperthermia, cardiac arrest, seizures, and trauma [3].Pressure myonecrosis or compartment syndromes may occur as a rare complication primarily in patients with prolonged unconsciousness and immobility as a result of drug abuse [2,4].
The patient described by Ulrich and colleagues took cocaine, benzodiazepines, and GBL (or GHB) and presented with rhabdomyolysis, acute compartment syndrome, and renal failure requiring surgical and intensive medical care.Cocaine use was confirmed by an urine drug screen.GBL use was not confirmed at admission to the hospital.Later, the patient admitted having used GBL, but it was then too late for a confirming analysis.Which of two drugs was responsible for the clinical picture?Cocaine has been widely reported to produce severe rhabdomyolysis [2,3] while GBL has never been mentioned to be associated with this adverse effect.In contrast, GBL has been shown to have interesting tissue-protective effects in a wide range of organ systems on a variety of animal and human models [5].GBL is therefore not expected to directly affect muscle tissue and to induce ischemic damage.As noted by Ulrich et al. we reported slightly increased levels of CK in patients with GBL intoxication (mean 626 U/l, range 176-1196) [6].This slight increase in CK possibly indicates that GBL drug users suffer from minor muscle cell damages due to immobilization while being comatose.We assume that the patient in the present case vignette suffered from severe immobilization trauma secondary to GBL induced coma.Thus, GBL use indirectly led to the observed muscle damage, possibly in addition to a first ischemic damage induced by cocaine use two days before.
What do we know about the combined use of GBL and cocaine?According to recent data from our hospital, cocaine was used in combination with GBL in 10 of 48 patients (21%) presenting with acute GBL poisoning

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Letter to the editor to our ED between 2001 and 2003.CK levels were (mean ± SD) 435 ± 701 U/l in 9 GBL mono-intoxicated patients and 420 ± 307 U/l in 8 patients with combined GBL and cocaine use.Thus, none suffered from a meaningful degree of rhabdomyolysis and the CK levels were not affected by cocaine use in this sample.However, we found that CK levels were positively correlated with the duration of coma in all patients (N = 30; Spearman R = 0,40; p <0.03) supporting the view that immobilization leads to increased levels of CK in these patients.Finally, we observed that the coabuse of stimulant drugs such as cocaine or Ecstasy with GBL resulted in significantly deeper and more prolonged coma compared with patients who used GHB or GBL alone.In summary, the combined use of GBL with stimulant drugs may increase the risk for rhabdomyolysis due to prolonged coma and immobilization in addition to the known risk of the stimulant drugs.
The case of Ulrich and colleagues illustrates the risk of an increasing trend of combined party drug use in our country.In addition, it underscores the need to take sufficient blood and urine samples at first presentation to be at hand for additional analytical workups.

Swiss Medical Weekly
The many reasons why you should choose SMW to publish your research Med Wochenschr (1871-2000) Swiss Med Wkly (continues Schweiz Med Wochenschr from 2001) Editores Medicorum Helveticorum but it has not yet been recognised as a potential lethal sequelae of GHB/GBL intoxication.