[Life-threatening metabolic acidosis after ingestion of fire extinguisher powder]. / Lebensbedrohliche Acidose nach Ingestion von ABC-Löschpulver.

We present the case of a 31-year old male with ingestion of fire extinguisher powder in an attempted suicide. After consulting several poison information centres, the intoxication was initially classified as harmless; nevertheless, the patient was admitted to our intensive care unit for cardiopulmonary monitoring. Subsequently, due to the ingestion of ammonium sulphate and ammonium dihydrogen phosphate containing powder the patient developed severe metabolic acidosis with distinct electrolyte imbalance that required temporary haemodialysis.

Alpha-gal is a possible target of IgE-mediated reactivity to antivenom.

BACKGROUND: Antivenoms are mammalian immunoglobulins with the ability to neutralize snake venom components and to mitigate the progression of toxic effects. Immediate hypersensitivity to antivenoms often occurs during the first administration of these heterologous antibodies. A comparable clinical situation occurred after introduction of cetuximab, a chimeric mouse-human antibody, for cancer treatment. The carbohydrate epitope galactose-alpha-1,3-galactose, located on the Fab region of cetuximab, was identified as the target responsible for IgE reactivity. OBJECTIVE: To investigate whether serum IgE antibodies directed to the α-gal epitope are associated with hypersensitivity to equine antivenoms. METHODS: Antivenoms were screened for α-gal epitopes via immunoblot and in comparison with cetuximab and pork kidney by IgE reactivity assays. Basophil activation tests were used to investigate reactivity to antivenoms in samples from 20 patients with specific IgE antibodies to α-gal and 10 controls. Additional IgE detection, IgE inhibition, ImmunoCAP inhibition, and skin prick tests were performed using samples from selected patients. RESULTS: Both antivenoms and cetuximab induced positive skin prick test results in patients with sIgE to α-gal. Alpha-gal epitopes were detected by immunoblotting on antivenoms. Measurements of IgE reactivity and ImmunoCAP inhibition indicated that the antivenoms contained lower α-gal contents than cetuximab. Deglycosylation assays and IgE inhibition tests confirmed that IgE-mediated reactivity to antivenom is associated with α-gal. Antivenoms, pork kidney, and cetuximab activated basophils from patients with IgE to α-gal. CONCLUSION: Alpha-gal is a potential target of IgE-mediated reactivity to equine antivenom and a possible cause of the high incidence of hypersensitivity reactions during the first application of equine antivenom.

Radial artery applanation tonometry for continuous non-invasive arterial pressure monitoring in intensive care unit patients: comparison with invasively assessed radial arterial pressure.

BACKGROUND: Radial artery applanation tonometry technology can be used for continuous non-invasive measurement of arterial pressure (AP). The purpose of this study was to evaluate this AP monitoring technology in intensive care unit (ICU) patients in comparison with invasive AP monitoring using a radial arterial catheter. METHODS: In 24 ICU patients (German university hospital), AP values were simultaneously recorded on a beat-to-beat basis using radial artery applanation tonometry (T-Line system; Tensys Medical, San Diego, CA, USA) and a radial arterial catheter (contralateral arm). The primary endpoint of the study was to investigate the accuracy and precision of the non-invasively assessed AP measurements with the Bland-Altman method based on averaged 10 beat AP epochs (n=2993 10 beat epochs). RESULTS: For mean AP (MAP), systolic AP (SAP), and diastolic AP (DAP), we observed a bias (±standard deviation of the bias; 95% limits of agreement; percentage error) of +2 mm Hg (±6; -11 to +15 mm Hg; 15%), -3 mm Hg (±15; -33 to +27 mm Hg; 23%), and +5 mm Hg (±7; -9 to +19 mm Hg; 22%), respectively. CONCLUSIONS: In ICU patients, MAP and DAP measurements obtained using radial artery applanation tonometry show clinically acceptable agreement with invasive AP determination with a radial arterial catheter. While the radial artery applanation tonometry technology also allows SAP measurements with high accuracy, its precision for SAP measurements needs to be further improved.

Non-invasive continuous arterial pressure measurement based on radial artery tonometry in the intensive care unit: a method comparison study using the T-Line TL-200pro device.

BACKGROUND: The T-Line TL-200pro (TL-200pro) device (Tensys Medical, Inc., San Diego, CA, USA), based on radial artery tonometry, provides an arterial pressure (AP) waveform and beat-to-beat values of systolic arterial pressure (SAP), mean arterial pressure (MAP), and diastolic arterial pressure (DAP). The aim of the study was to evaluate this non-invasive technique for continuous AP monitoring in medical intensive care unit (ICU) patients. METHODS: Arterial pressure measurements obtained using the TL-200pro technology were compared using Bland-Altman analysis with values measured directly from a femoral arterial catheter in 34 ICU patients. RESULTS: Arterial pressure values were analysed and compared in 4502 averaged 10-beat epochs. A bias of +0.72 mm Hg (95% limits of agreement -9.37 to +10.82 mm Hg) was observed for MAP. For SAP and DAP, there was a mean difference of -1.39 mm Hg (95% limits of agreement -18.74 to +15.96 mm Hg) and +4.36 mm Hg (95% limits of agreement -8.66 to +17.38 mm Hg), respectively. The percentage error for MAP, SAP, and DAP was 12%, 14%, and 21%, respectively. CONCLUSIONS: Arterial pressure measurement based on radial artery tonometry using the TL-200pro technology is feasible in medical ICU patients. The TL-200pro system is capable of providing MAP values with high accuracy (low mean difference) and precision (narrow limits of agreement) compared with MAP measured invasively using a femoral arterial catheter. The TL-200pro technology is promising for the measurement of SAP and DAP but further development is necessary to improve accuracy and precision.

Stenotrophomonas maltophilia in the respiratory tract of medical intensive care unit patients.

The purpose of this study was to investigate characteristics of critically ill patients with Stenotrophomonas maltophilia (S. maltophilia) isolated from the respiratory tract, to identify risk factors for S. maltophilia-pneumonia and intensive care unit (ICU) mortality and to analyze antibiotic susceptibility of S. maltophilia. This was a retrospective analysis of 64 medical ICU patients with S. maltophilia in the respiratory tract. Thirty-six patients fulfilled the criteria for diagnosis of pneumonia. A significantly higher lung injury score (LIS) was observed in patients with pneumonia compared to patients with colonization (p=0.010). Independent risk factors for S. maltophilia-pneumonia were higher Sequential Organ Failure Assessment (SOFA) score (p=0.009) and immunosuppression (p=0.014). Patients with S. maltophilia-pneumonia had higher ICU mortality within a 28-day follow-up (p=0.040) and higher hospital mortality (p=0.018) than patients with colonization. The highest antibiotic susceptibility rates were observed to trimethoprim-sulfamethoxazole, tigecycline, and moxifloxacin. Higher SOFA score when S. maltophilia was isolated (p=0.001) and development of renal failure (p=0.021) were independent risk factors for ICU mortality. Higher SOFA score and immunosuppression are independent risk factors for S. maltophilia-pneumonia. Patients with S. maltophilia-pneumonia have a significantly higher ICU mortality within a 28-day follow-up, hospital mortality and LIS compared to patients with S. maltophilia-colonization.

Pharmacokinetics of obidoxime in patients poisoned with organophosphorus compounds.

OBJECTIVES: Reactivation of inhibited acetylcholinesterase (AChE) with oximes is a causal therapy of intoxication with organophosphorus compounds (OPs). Maximal oxime effects are expected when effective doses are administered as soon as possible and as long as reactivation can be anticipated. An obidoxime plasma level in the range of 10-20 microM was estimated as appropriate. The achievement of this target was assessed in 34 severely OP-poisoned patients. METHODS: After admission to the intensive care unit (ICU) the obidoxime regimen (250 mg i.v. as bolus, followed by 750 mg/24h) was started and maintained as long as reactivation was possible. Plasma concentrations of obidoxime were determined by HPLC. RESULTS: A total amount of 2269+/-1726 mg obidoxime was infused over 65 h+/-55 h resulting in a steady state plasma concentration of 14.5+/-7.3 microM. Obidoxime was eliminated with t(1/2(1)) 2.2 and t(1/2(2)) 14 h. The volumes of distribution amounted to 0.32+/-0.1L/kg (V((1))) and 0.28+/-0.12 (V((2)))L/kg. Postmortem examination of tissue in one patient showed obidoxime accumulation in cartilage, kidney and liver and pointed to brain concentrations similar to plasma concentration. CONCLUSIONS: Using the suggested obidoxime regimen, the targeted plasma concentration could be achieved. Obidoxime was eliminated biphasically and was well tolerated. This result allows the recommendation of using this definite regimen for adults also in case of mass casualties.

[Lead intoxication in a group of workers in Germany]. / Gruppenvergiftung mit Blei am Arbeitsplatz.

HISTORY AND ADMISSION FINDINGS: Seventeen East-European workers with a suspected lead-intoxication presented themselves to the Department of Toxicology. All of them had worked on the renovation of pylons of a high-tension line. The old paint, known to contain lead was removed with needle descalers. The patients had blood lead concentrations between 325 and 1124 microg/l, but no specific symptoms. The workers neglected the protective measures at their working-place. INVESTIGATIONS: 12 of 17 workers had lead-concentrations above 400 microg/l (Reference < 90 microg/l). 10 of 17 patients showed an increased level of free protoporphyrins and all workers showed a decreased activity of delta-aminolaevulinacid-dehydratase (ALAD). TREATMENT AND COURSE: Patients with lead-concentration above 700 microg/l were treated with the chelating agent meso-2,3-dimercaptosuccinic acid (DMSA) 3 x 200 mg/d for nine days. The patients with lead concentrations between 400 and 700 microg/l were treated which DMSA 3 x 100 mg/d. After the DMSA-treatment the lead-concentrations had dropped (p < 0.001). During the DMSA-therapy one patient had to be treated in the hospital because of a generalised allergic exanthema. CONCLUSION: We report seventeen patients with high lead concentration in their blood due to occupational exposure. The high blood lead levels showed that the workers had not been protected adequately. This examplifies that occupational lead exposure still occurs, also in Germany. By patients with unspecific symptoms connected with lead exposure a biomonitoring for lead is necessary.

Monitoring of neuromuscular transmission in organophosphate pesticide-poisoned patients.

Thirty-four adult patients with severe organophosphorus compounds (OP) poisoning requiring artificial ventilation were enrolled in a clinical study and received atropine and obidoxime (250 mg i.v., followed by 750 mg/24 h) as antidotal treatment. Here, we re-analyzed the cholinesterase status (red blood cell acetylcholinesterase (RBC-AChE) activity, reactivatability of RBC-AChE, and plasma butyrylcholinesterase (Pl-BChE) activity) in relation to the neuromuscular transmission (NMT) data. When RBC-AChE activity ranged between 100% and 30% NMT was unimpaired after tetanic stimulation with frequencies up to 50 Hz. A further decrease in RBC-AChE activity was accompanied by a marked disturbance of NMT, being strongly impaired at AChE activities <5% of normal. Higher stimulation frequencies (>30 Hz) facilitated the discrimination of the types of impairment. The neuromuscular transmission was the best quantified by using the ratio of the ninth to the first amplitude, while the standard method was less discriminative. At RBC-AChE levels higher than 40% of normal weaning from the ventilator may be considered. Completely aged RBC-AChE as indicated by loss of reactivatability loses its guidance function. Then, steadily increasing Pl-BChE activity suggests lack of circulating poison. One-week later, neuromuscular transmission may be largely normal and patients could be weaned from the respirator if other complications are not withstanding.

Acute effects of sulfur mustard injury--Munich experiences.

Sulfur mustard (SM) is a strong vesicant agent which has been used in several military conflicts. Large stockpiles still exist to the present day. SM is believed to be a major threat to civilian populations because of the persistent asymmetric threat by non-state actors, such as terrorist groups, its easy synthesis and handling and the risk of theft from stockpiles. Following an asymptomatic interval of several hours, acute SM exposure produces subepidermal skin blisters, respiratory tract damage, eye lesions and bone marrow depression. Iranian victims of SM exposure during the Iran-Iraq (1984-1988) war were treated at intensive care units of 3 Munich hospitals. All 12 patients were injured following aerial attacks with SM filled bombs, which exploded in a distance between 5 and 30m. All patients soon noted an offensive smell of garlic, addle eggs or oil roasted vegetables. No individual protective equipment was used. Eye itching and skin blistering started 2h after SM exposure. Some patients complained of nausea, dizziness and hoarseness. 4h after exposure, most patients started vomiting. Eye symptoms worsened and most patients suffered from temporary blindness due to blepharospasm and lid oedema. Additionally, pulmonary symptoms such as productive cough occurred. Patients were transferred to Munich 4-17 days after SM exposure. On admission all patients showed significant skin blistering and pigmentation. Conjunctivitis and photophobia were the major eye symptoms. Pulmonary symptoms, including productive cough were persistent. Bronchoscopy revealed massive inflammation of the trachea with signs of necrosis. 3 patients needed tracheotomy. Chest X-ray did not yield abnormal observations. This presentation summarizes the experience of treating SM victims in Munich and discusses therapeutic implications.

Suitability of human butyrylcholinesterase as therapeutic marker and pseudo catalytic scavenger in organophosphate poisoning: a kinetic analysis.

The widespread use of organophosphorus compounds (OPs) as pesticides and the frequent misuse of OP nerve agents in military conflicts or terrorist attacks emphasize the high clinical relevance of OP poisoning. The toxic symptomatology is caused by inhibition of acetylcholinesterase (AChE). A mainstay of standard antidotal treatment is atropine for antagonizing effects mediated by over stimulation of muscarinic ACh-receptors and oxime to reactivate OP-inhibited AChE. For therapeutic monitoring of oxime treatment in OP poisoning, measurement of erythrocyte AChE is suitable because erythrocyte AChE is an easily accessible surrogate for synaptic AChE. However, measurement of erythrocyte AChE is not standard practice. In contrast, determination of plasma butyrylcholinesterase (BChE) activity is in routine use for monitoring the benefit of oxime therapy. As oxime efficacy is limited with certain OPs (e.g. dimethoate, tabun, soman) alternative therapeutic approaches, e.g. the application of scavengers (BChE) which may sequester OPs before they reach their physiological target, are under investigation. To assess the eligibility of BChE as laboratory parameter and (pseudo catalytic or stoichiometric) scavenger in OP poisoning we initiated an in vitro study under standardized experimental conditions with the objective of determination of kinetic constants for inhibition, reactivation and aging of plasma BChE. It could be shown that, due to limited efficacy of obidoxime, pralidoxime, HI 6 and MMB4 with OP-inhibited BChE, plasma BChE activity is an inappropriate parameter for therapeutic monitoring of oxime treatment in OP poisoning. Furthermore, oxime-induced reactivation is too slow to accomplish a pseudo catalytic function, so that administered BChE may be merely effective as a stoichiometric scavenger.

Acute renal failure by ingestion of Cortinarius species confounded with psychoactive mushrooms: a case series and literature survey.

Mushrooms of the Cortinarius species are nephrotoxic and can cause severe acute renal failure. The toxic effect is due to orellanine. It is suspected that the cytotoxic damage is caused by the production of oxygen-free radicals. Renal pathology shows tubular necrosis with interstitial nephritis. In addition to accidental intoxications as a consequence of mushroom meals, recent cases are often due to voluntary abuse of natural drugs like magic mushrooms. We report 4 current cases of acute renal failure from intoxication by Cortinarius species by confusing it with psychoactive fungi. Typical for the Cortinarius poisoning is the long latency period from ingestion until the onset of clinical symptoms (3 - 20 days). Diagnosis is based on microscopical identification of the mushroom spores, and detection of the orellanine toxin in leftover mushrooms. In renal biopsy tissue, orellanine is detectable by thin-layer chromaography technique up to 6 months after poisoning. There is no causative therapy, and treatment is symptomatic with adequate hemodialysis. In cases of otherwise unexplained acute renal failure, intoxication with nephrotoxic mushrooms should be considered.

[Amanita poisoning--comparison of silibinin with a combination of silibinin and penicillin]. / Knollenblätterpilzvergiftung. Silibinin und Kombination von Silibinin und Penicillin im Vergleich.

BACKGROUND AND AIMS: Current treatment of amatoxin poisoning includes the administration of silibinin and penicillin in combination or silibinin alone. The aim of this study was to compare both therapeutic regimes. PATIENTS AND METHODS: Of 604 patients with the suspected diagnosis of amatoxin poisoning 367 were retrospectively analysed: 118 patients had received silibinin alone and 249 patients silibinin in combination with penicillin. Logistic regression analyses were applied to investigate the efficacy of both therapeutic regimens by comparing death and liver transplantation rates. A potentially independent effect on outcome of age, sex, year of treatment, latency period of symptoms and start of silibinin therapy was taken into account. RESULTS: In the group who had received the combination of silibinin and penicillin 8.8% died or underwent liver transplantation compared to 5.1% in the group of those who had received silibinin alone. The risk of death or organ transplantation was thus reduced by nearly 40% in the latter group (adjusted odds ratio: 0.58; 95% CI: 0.21-1.57; p=0.28). A longer latency period (< or =12h vs. >12h) was associated with a significant reduction of this risk (adjusted OR.: 6.10; 95% CI:1.77-21.3; p=0.004). A later start of silibinin therapy (>24h vs. < or = 24h) was associated with a tendency toward an increased frequency of death or organ transplantation (adjusted OR.: 3.0; 95% CI: 0.96-9.20; p=0.059). CONCLUSIONS: A lower death and transplantation rate was observed in the silibinin treatment group than in group treated with silibinin combined with penicillin. However, this difference was not statistically significant. The high risk ratio relating to the time-dependent effect of silibinin suggests its efficaciousness in the treatment of amatoxin poisoning. The latency period was assessed as an independent prognostic factor.

Withdrawal from high-dose tranylcypromine.

A 34-year-old man with a history of multiple substance abuse (now abstinent for six years) became addicted to tranylcypromine, consuming up to 240 mg/day. After discontinuing the drug, he developed thrombocytopenia (52,000/ul) and delirium; there were no other anticholinergic signs. The delirium was unresponsive to haloperidol and diazepam. Intravenous administration of physostigmine (2 mg) on hospital day 6 resulted in prompt, but temporary, clearing of the delirium. Following a recurrence of the delirium after 30 minutes, he was started on an intravenous infusion of physostigmine (2 mg/hr) with good results. Physostigmine administration did not produce any cholinergic signs. By hospital day 8, he did not require any more physostigmine. Thrombocytopenia resolved on hospital day 9 without therapeutic intervention. On hospital day 10, the patient was asymptomatic and left the hospital on his own recognizance.

[Attempted suicide by snake bite. Case report and literature survey]. / Suizidversuch durch Schlangenbiss. Kasuistik und Literaturübersicht.

Unusual suicide attempts often remain undetected, and bizarre methods can be a clue to psychotic origin. We report a suicide attempt by proxy--the bite of a puff adder--and provide a brief literature survey about further archaic self-injurious behaviour. Due to the easy availability of venomous snakes and the close networking of suicidal patients via the Internet, an increase in similar cases can be anticipated. A failed suicide attempt should always be considered in patients surviving bizarre accidents.

Cause and motivation in cases of non-fatal drug overdoses in opiate addicts.

INTRODUCTION: Drug overdose (OD) is a frequent incident among opiate addicts. Survivors of ODs are at risk for additional and eventually fatal ODs. ODs may be classified as accidental (aOD) or deliberate (dOD). Investigations into the connection between OD and suicide attempts have led to insconsistent results. PURPOSE: (1) to determine how many non-fatal ODs were dODs and how many were aODs; (2) to determine how many cases of dODs were motivated by explicit or by ambivalent suicidal intentions; (3) to determine how many cases of aODs had causes that might respond to preventative measures; (4) to compare the addiction histories of dODs and aODs; (5) to compare the drugs causing the ODs; and (6) to compare the severity of the ODs in both groups. METHODS: Prospective study utilizing a standardized questionnaire to evaluate opiate-addicted patients admitted to our treatment unit for OD. All cases underwent standardized drug testing to identify drug use patterns. RESULTS: Seventy-four cases of OD underwent standardized interviews after awakening. Forty-three percent of the cases were dOD. Cases of dOD had significantly more OA in substitution programs, more previous ODs, and more often consumed methadone and cocaine. Among dODs, 22.5% had suicidal intention and 9.6% were ambivalent about committing suicide; background motivations were most often conflicts with spouses. Fifty-seven percent of the cases were aOD. Cases of aODs had significantly more potential lethal intoxications and had heroin detected more frequently. aODs happened with unexpected pure heroin (46%), in combination with alcohol (36%), as relapse after abstinence (40%) or after institutionalized treatment (19%). This group should be accessible for targeted education.

[Lethal sepsis and multi-organ failure after accidental injection of urine in a drug addict]. / Letal verlaufende Sepsis und Multiorganversagen nach akzidenteller Urin-Injektion bei einer drogenabhängigen Patientin.

HISTORY AND ADMISSION FINDINGS: A 33-year-old drug addict injected accidentally into the femoral vein 5 ml urine (kept in the refrigerator for 1 week for unanticipated drug-screening) which she mis-took for methadone. Soon after injection she was found confused with shivering. On admission she had a blood pressure of 90/60 mmHg, heart rate of 120/min and fever of 40 degrees C. INVESTIGATIONS: Laboratory tests showed consumption coagulopathy (DIC) as well as leukopenia. Blood cultures were positive for E.coli and Klebsiella pneumoniae. Infection with hepatitis C and HIV was excluded. Echocardiography revealed good ventricular function without signs of endocarditis. DIAGNOSIS AND TREATMENT: The patient developed a fulminant Gram-negative sepsis with DIC and multi-organ failure. She was intubated and mechanically ventilated. Acute renal failure required haemodialysis and ultrafiltration. Septic shock was treated with fluids and high doses of vasopressors. DIC was effectively treated with tranexamic acid, PPSB complex and fresh frozen plasma. The further course was complicated by septic emboli to the myocardium, liver, kidney and spleen. Laparotomy because of an acute abdomen revealed perforation of terminal ileum (mainly due to ischemic bowel lesions) requiring partial resection. The patient was weaned on day 18 with an initially uneventful further course. On day 25 the patient had a cardiac arrest with at first successful resuscitation but electromechanical dissociation proved fatal on day 26. CONCLUSION: Although serious systemic inflammation associated with i. v.-injection in drug addicts is rare, one has to be aware of severe complications with septic emboli. To our knowledge it is the first published case of i. v.-injection of urine followed by sepsis and multi-organ failure. Aggressive interdisciplinary treatment is required.

[The development of a toxic megacolon due to Amanita phalloides poisoning. A rare complication]. / Die Entwicklung eines toxischen Megakolons bei Knollenblätterpilzvergiftungen - Eine ungewöhnliche Komplikation -

HISTORY: A 71-year-old previously healthy man consumed a mushroom meal containing Amanita phalloides, which he had confused with Agaricus campestris. Approximately 8 hours later, typical gastrointestinal symptoms began with copious loss of fluids. Treatment with penicillin G was initiated followed by a continuous silibinin infusion before the patient was transferred to our toxicological department. Other than a transient tachycardia and diffuse pain on abdominal palpation clinical examination was without abnormal findings. INVESTIGATIONS: Laboratory findings showed severe hepatic damage with 100-fold increased transaminases, elevation of serum creatinine, hyperbilirubinemia and a serious disturbance of coagulation. Infection with HIV, hepatitis- and CMV as well as pathogenic enteric bacteria and antibiotic-associated pseudo-membranous colitis were excluded. 11 days after the mushroom meal x-ray of abdomen showed a 6 cm dilatation of the small intestine and an 8 cm dilatation of the colon. DIAGNOSIS AND TREATMENT: Although clinical condition and laboratory findings nearly fulfilled transplantation criteria, hepatic injury resolved during intensive care therapy. Intractable diarrhea, dilatation of the intestine on x-ray as well as other findings met criteria of toxic megacolon. Therapy with antibiotics and systemic steroids was ineffective, so the patient needed decompression by a catheter, which was placed by colonoscopy. 30 days after the serious amanita poisoning complicated by development of toxic megacolon, the patient's condition resolved without sequelae and he was discharged. CONCLUSIONS: In addition the well known complications of amanita-poisoning, such as hepatic failure, encephalopathy and multi-organ failure, involvement of other organs like bone marrow, pancreas, kidney and gastrointestinal tract (except for the initial cholera-like gastroenteritis) are not well documented in the literature. Uncommon complications like toxic megacolon require an empirical approach.