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IntroductionTraumatic brain injury (TBI) is the leading cause of mortality and long-term disability in young adults. Despite the high prevalence of anaemia and red blood cell transfusion in patients with TBI, the optimal haemoglobin (Hb) transfusion threshold is unknown. We undertook a randomised trial to evaluate whether a liberal transfusion strategy improves clinical outcomes compared with a restrictive strategy.Methods and analysisHEMOglobin Transfusion Threshold in Traumatic Brain Injury OptimizatiON is an international pragmatic randomised open label blinded-endpoint clinical trial. We will include 742 adult patients admitted to an intensive care unit (ICU) with an acute moderate or severe blunt TBI (Glasgow Coma Scale ≤12) and a Hb level ≤100 g/L. Patients are randomly allocated using a 1:1 ratio, stratified by site, to a liberal (triggered by Hb ≤100 g/L) or a restrictive (triggered by Hb ≤70 g/L) transfusion strategy applied from the time of randomisation to the decision to withdraw life-sustaining therapies, ICU discharge or death. Primary and secondary outcomes are assessed centrally by trained research personnel blinded to the intervention. The primary outcome is the Glasgow Outcome Scale extended at 6 months. Secondary outcomes include overall functional independence measure, overall quality of life (EuroQoL 5-Dimension 5-Level; EQ-5D-5L), TBI-specific quality of life (Quality of Life after Brain Injury; QOLIBRI), depression (Patient Health Questionnaire; PHQ-9) and mortality.Ethics and disseminationThis trial is approved by the CHU de Québec—Université Laval research ethics board (MP-20-2018-3706) and ethic boards at all participating sites. Our results will be published and shared with relevant organisations and healthcare professionals.Trial registration numberNCT03260478.

A recent report by the Chief Public Health Officer of Canada demonstrates the inferior health status of Indigenous Peoples in Canada when compared to non-Indigenous populations. This scoping review maps out the available literature concerning acute health care for Indigenous Peoples in Canada in order to better understand the health care issues they face. All existing articles concerning health care provided to Indigenous Peoples in Canada in acute settings were included in this review. The targeted studied outcomes were access to care, health care satisfaction, hospital visit rates, mortality, quality of care, length of stay and cost per hospitalisation. 114 articles were identified. The most studied outcomes were hospitalisation rates (58.8%), length of stay (28.0%), mortality (25.4%) and quality of care (24.6%) Frequently studied topics included pulmonary disease, injuries, cardiovascular disease and mental illness. Indigenous Peoples presented lower levels of satisfaction and access to care although they tend to be over-represented in hospitalisation rates for acute care. Greater inclusion of Indigenous Peoples in the health care system and in the training of health care providers is necessary to ensure a better quality of care that is culturally safe for Indigenous Peoples.

Managing unstable poisoned patients is often associated with clinician cognitive overload. This article summarizes the mechanisms of toxicity; clinical presentations; and the current evidence available for the treatment of cardiovascular drug toxicity due to calcium channel blockers, beta-blockers, cardiac glycosides, and sodium channel blockers. In addition, management approaches are proposed.

Purpose: This study aimed to define the behavioral determinants influencing the decision of intensivists to consult a poison center (PC) when managing patients with calcium channel blocker (CCB) poisoning. Material and methods: Semi-structured interviews were conducted involving a convenience sample of 18 intensivists. Two independent reviewers analyzed the interview responses using the Theoretical Domains Framework. Based on the impact and frequency of the reported behaviors, we selected the most relevant domains likely to influence intensivists’ decision to consult a PC for CCB poisoning. Results: Beliefs influencing physicians positively to consult a PC for CCB poisoning were identified in the following domains: knowledge (e.g., lower level of evidence), social or professional role and identity (e.g., high credibility attributed to the PC), reinforcement (e.g., multiple drug poisoning, infrequent or potentially lethal poisoning, medicolegal considerations), and behavioral regulation (e.g., facilitated access of PC to patient’s hospital chart, direct communication with a toxicologist). Beliefs deterring physicians from consulting a PC for CCB poisoning were identified in the following domains: knowledge (e.g., better awareness of recommendations decreases tendency to call), goals (e.g., priority for patient stabilization), and memory, attention, and decision process (e.g., cognitive overload due to an unstable patient). Conclusion: This qualitative study identified potential behavioral targets that future implementation strategies should address to improve collaboration between PCs and intensivists. In light of our results, the Québec PC now asks clinicians if the poisoned patient is unstable prior to collecting any other information. When necessary, a teleconference with the toxicologist is proposed earlier than before.

This report describes a rare but life-threatening case of a suicide attempt initially considered as intentional overdose at the emergency department. Persistent altered mental status, despite normal toxicology investigations, led the attending team to order a head computed tomography scan, which revealed a bilateral penetrating nail gun injury with a right temporal hematoma for which a decompressive craniectomy was performed. Although voluntary intoxication is the most frequent form of suicide attempt, emergency physicians must be alert and maintain a broad differential diagnosis. Although rare, penetrating head injuries have increased in recent decades. As neurological symptoms can be minimal and penetration wounds small, this type of injury could potentially be overlooked.

We describe the case of a 52-year-old man who presented after having ingested an unknown quantity of phenytoin. Peak phenytoin concentration was 51.2 mg/L (therapeutic range 10-20 mg/L). Five days after admission, the patient became comatose and was intubated. Because of persistent toxic phenytoin levels and unchanged clinical status for 12 days, hemodialysis (HD) was prescribed to enhance elimination of phenytoin. HD was performed using a Gambro TheraliteTM filter (Baxter International Inc., Deerfield, USA), a high cut-off filter that allows the removal of molecules of up to 45 kDa. Phenytoin concentration readily decreased during the 8-hour HD treatment from 38.9 mg/L to 27.8 mg/L (28.5% decrease); during HD, phenytoin half-life was 18.5h (compared to 1109.8h before HD and 56.3h after HD), phentyoin clearance averaged 80.1 mL/min and a total of 1.1 g of phenytoin was removed. Albumin removal from the Theralite filter was most important at the beginning of HD. The high clearance of phenytoin obtained with this filter was likely due to its high surface area rather than its capacity to remove the albumin-phenytoin complex.

Background: A study published by St-Onge at al. (2012), identified an important variation in practice in regards to the management of calcium channel blocker (CCB) poisoning.

Older adults are at increased risk of atrial fibrillation (AF), its thromboembolic complications, and bleeding. A significant percentage of octogenarians do not receive anticoagulation therapy. The objective of this study was to investigate the effect of thromboembolic risk, bleeding risk, and frailty on the anticoagulation status of octogenarians hospitalized with AF.A cross-sectional study was conducted in 682 hospitalized patients aged 80 years and older with AF or atrial flutter in Montreal, Québec. Consumption of warfarin or a new oral anticoagulant was documented. Medical record data were used to determine each patient's frailty status using the Clinical Frailty Scale (CFS) and to evaluate the risk of stroke (CHADS2 [Congestive Heart Failure, Hypertension, Age, Diabetes, Stroke/Transient Ischemic Attack]) and bleeding (HAS-BLED [Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly ( 65 years) Drugs/alcohol concomitantly]). Univariable and multivariable logistic regression analyses were used to examine the effect of frailty status and the risk of stroke and bleeding on the probability of receiving anticoagulation therapy.Seventy percent of octogenarians with AF received anticoagulation therapy (n = 475). A high risk of stroke (CHADS2 = 3 compared with CHADS2 = 1, odds ratio [OR], 3.58; 95% confidence interval [CI], 1.09-11.77), and the absence of severe frailty (CFS7; OR, 3.41; 95% CI, 1.84-6.33) were independently associated with anticoagulant use in multivariable analyses. A high risk of bleeding (HAS-BLED score ≥ 3; OR, 0.33; 95% CI, 0.12-0.86) was associated with the absence of anticoagulation.Our study suggests a higher prevalence of appropriate anticoagulation among octogenarians with AF than reported in previous studies. Further work is needed to develop and disseminate tools to optimize the use of anticoagulants in this high-risk population.

Introduction: Cardiotoxicants poisonings are rare but have the potential to be highly lethal. Given the precarious nature of these poisonings, the Quebec Poison Control Center (CAPQ) has established a management protocol for optimal treatment. This study seeks to evaluate whether CAPQ's Calcium Channel Blocker (CCB) poisoning management protocol improves treatment delivery by physicians using simulation. The primary outcome is whether the management protocol decreases time to delivery of calcium and insulin. The secondary outcome is whether use of the management protocol increases appropriate dosing. Methods: For this randomized AB / BA crossover trial, Emergency Medicine and Internal Medicine residents were randomly assigned to one of two groups; one group received the management protocol during the simulation and the other did not. The crossover occurred 3-months later whereby the groups were reversed. Inverse probability weighting was used to compensate for losses at follow-up. Differences in baseline characteristics, as well as carry-over effect, were evaluated. The outcomes were analyzed with a two-level hierarchical model. Results: Twenty-three residents were included in the study. No significant differences in baseline characteristics were noted between the AB / BA groups, and no carry-over effect was identified on statistical analysis for all variables. As for the primary outcomes, time to administration of IV calcium decreased by 87 seconds (CI -266 to 92), time to insulin bolus decreased by 52 seconds (-217 to 114), and time to insulin infusion decreased by 115 seconds (-213 to -18) when the protocol was used. As for the secondary outcomes, there were no statistically significant differences for the percentage of adequate doses of IV calcium (RR: 1.27; 95% CI: 0.80–2.02), insulin bolus (RR: 1.30; 95% CI: 0.80–2.12) and insulin infusion (RR: 1.37; 95% CI: 0.99–1.91). Conclusion: This randomized cross-over study, which uses simulation to evaluate the performance of CAPQ's CCB poisoning management protocol, does not statistically demonstrate decreased time to administration or increased accuracy of dosing, due to the large confidence intervals. Unfortunately, we were not able to obtain the planned sample size due to limited participation. However, our results trend towards more optimal dosing and rapid dosing of treatments, and from a qualitative standpoint, the protocol appeared to increase the structure of patient care.

Objective This study examined the association between the administration of drugs to the wrong nursing home residents with a need for hospital treatment or as an indicator of mortality. Design A retrospective observational study of medical records from February 1, 2016, to January 31, 2017. Setting Calls made to the Quebec Poison Center. Participants Nursing home residents aged ≥65 years. Intervention(s) Medication administered to the wrong resident. Main Outcome Measure(s) Death, hospital referral and treatment, number of drugs or type of drug classes. Results Of the 6282 calls received by the Quebec Poison Center concerning medication errors, 494 cases were included in the retrospective study. Half of the patients (51%) received at least 5 different drugs that were not prescribed for them. Most patients (82%) were asymptomatic at the time of the call to the poison center; however, a third (34%) of the exposures were considered potentially toxic and were treated at the hospital. The most prominent drug classes involved include antihypertensives, antiarrhythmics, and antipsychotics. In particular, almost a quarter (23%) of cases of clozapine maladministration resulted in moderate or severe effects. No deaths were reported. Conclusions/Implications Medication errors in nursing homes are prevalent. The medical provider and probably the poison control center should be consulted as soon as possible when people are aware of administration of medication to the wrong patient, which is considered a medical emergency until proven otherwise. Public policies should seek for better surveillance and prompt intervention. Research should be undertaken to limit errors of drug administration to the wrong nursing home residents.

What you need to know Is the needle tip configuration important when performing a lumbar puncture for any indication? A systematic review published in the Lancet in December 2017 suggests that it is. The review found that using atraumatic (pencil-point) lumbar puncture needles instead of conventional lumbar puncture needles reduced the risk of post-dural-puncture headache and of return to hospital for additional pain control.1 This guideline recommendation aims to promptly and transparently translate this evidence to a clinical recommendation, following standards for GRADE methodology and trustworthy guidelines.2 The BMJ Rapid Recommendations panel makes a strong recommendation for the use of atraumatic needles for lumbar puncture in all patients regardless of age (adults and children) or indication instead of conventional needles.34 Box 1 shows the article and evidence linked to this Rapid Recommendation. The main infographic provides an overview of the absolute benefits and harms (although none were present here) of atraumatic needles. Table 1 below shows any evidence that has emerged since the publication of this guideline. Box 1 ### Linked resources for this BMJ Rapid Recommendations clusterRETURN TO TEXT

A short cut review was carried out to see if the presence of ‘B lines’ detected on lung ultrasound could be used to guide the volume of fluid replacement necessary in the resuscitation of the patient with sepsis. Four papers with some degree of relevance were found in the literature search. The author, date and country of publication, patient group studied, study type, relevant outcomes, results study weaknesses of these papers are tabulated. Although a promising concept, the remains a paucity of good quality evidence sufficient to recommend this approach.

Supplemental Digital Content is available in the text., Objective: To provide a management approach for adults with calcium channel blocker poisoning. Data Sources, Study Selection, and Data Extraction: Following the Appraisal of Guidelines for Research & Evaluation II instrument, initial voting statements were constructed based on summaries outlining the evidence, risks, and benefits. Data Synthesis: We recommend 1) for asymptomatic patients, observation and consideration of decontamination following a potentially toxic calcium channel blocker ingestion (1D); 2) as first-line therapies (prioritized based on desired effect), IV calcium (1D), high-dose insulin therapy (1D–2D), and norepinephrine and/or epinephrine (1D). We also suggest dobutamine or epinephrine in the presence of cardiogenic shock (2D) and atropine in the presence of symptomatic bradycardia or conduction disturbance (2D); 3) in patients refractory to the first-line treatments, we suggest incremental doses of high-dose insulin therapy if myocardial dysfunction is present (2D), IV lipid-emulsion therapy (2D), and using a pacemaker in the presence of unstable bradycardia or high-grade arteriovenous block without significant alteration in cardiac inotropism (2D); 4) in patients with refractory shock or who are periarrest, we recommend incremental doses of high-dose insulin (1D) and IV lipid-emulsion therapy (1D) if not already tried. We suggest venoarterial extracorporeal membrane oxygenation, if available, when refractory shock has a significant cardiogenic component (2D), and using pacemaker in the presence of unstable bradycardia or high-grade arteriovenous block in the absence of myocardial dysfunction (2D) if not already tried; 5) in patients with cardiac arrest, we recommend IV calcium in addition to the standard advanced cardiac life-support (1D), lipid-emulsion therapy (1D), and we suggest venoarterial extracorporeal membrane oxygenation if available (2D). Conclusion: We offer recommendations for the stepwise management of calcium channel blocker toxicity. For all interventions, the level of evidence was very low.

A shortcut review was carried out to establish whether silibinin is better than conservative management at reducing liver transplantation and death after poisoning with amatoxin-containing mushrooms. Thirty-eight papers were found in Medline and 86 in EMBASE using the reported searches. Of these, five presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. It is concluded that the evidence is limited, but given the lack of alternative treatments in patients with suspected amatoxin-containing mushroom poisoning and the relatively few adverse effects, silibinin should be considered in some patients.

BACKGROUND: For training programs to meet the needs of trainees, an understanding of their career goals and expectations is required.OBJECTIVES: Canadian critical care medicine (CCM) trainees were surveyed to understand their career goals in terms of clinical work, research, teaching, administration and management; and to identify their perceptions regarding the support they need to achieve their goals.METHODS: The online survey was sent to all trainees registered in a Canadian adult or pediatric CCM program. It documented the participants’ demographics; their career expectations; the perceived barriers and enablers to achieve their career goals; and their perceptions relating to their chances of developing a career in different areas.RESULTS: A response rate of 85% (66 of 78) was obtained. The majority expected to work in an academic centre. Only approximately one-third (31%) estimated their chances of obtaining a position in CCM as >75%. The majority planned to devote 25% to 75% of their time performing clinical work and CONCLUSION: CCM trainees perceived having only limited support to help them to achieve their career goals and anticipate difficulties in obtaining successful employment. They identified several gaps that could be addressed by training programs, including more mentoring in the areas of research, education and administration.

Oxycodone is an opioid agonist largely prescribed for the treatment of moderate to severe pain. Variability in analgesic efficacy could be explained by inter-subject variations in plasma levels of parent drug and its active metabolite, oxymorphone. For this purpose it is necessary to develop and validate a sensitive and selective analytical method for the quantification of oxycodone and its major metabolites, noroxycodone and oxymorphone, in human plasma. The analytical method consisted of a liquid-liquid extraction procedure followed by a high performance liquid chromatography with heated assisted electrospray ionization mass spectrometry (HPLC-HESI-MS/MS). The chromatographic separation was achieved using gradient elution with a mobile phase consisting of ethanol and 10mM ammonium acetate on a Synergi MAX-RP analytical column (150×2mm, 4μm) protected by a security guard cartridge (C12 4×2mm) at a flow rate of 300μL/min.The calibration functions are linear in the range of 300-50,000pg/mL for oxycodone and noroxycodone and 50 to 10 000pg/mL for oxymorphone. Intra- and inter-day relative standard deviations are less than 5.5% and 6.4%, respectively for all analytes. The limit of detection was 30pg/mL for all analytes. We introduce a new HPLC-HESI-MS/MS sensitive and specific analytical method capable to simultaneously quantify oxycodone, noroxycodone and oxymorphone, in human plasma, and suitable for the conduct of pharmacokinetic studies after a single dose administration of the parent compound.

Patient: Male, 70 Final Diagnosis: Thyroid storm Symptoms: Atrial fibrillation • confusion • hyperthermia • tachycardia Medication: — Clinical Procedure: Intubation • cardioversion Specialty: Critical Care Medicine Objective: Adverse events of drug therapy Background: We report a case of thyroid storm caused by consuming a Chinese herb contaminated with thyroid hormones. Case Report: A 70-year-old man presented to an emergency department after 2 days of nausea, vomiting, and weakness. Three days previously, he had started taking Cordyceps powder and “Flower Man Sang Hung” as recommended by his Chinese physician. Following admission, the patient deteriorated and was eventually diagnosed with thyroid storm complicated by rapid atrial fibrillation requiring cardioversion, intubation, and intensive care admission. The analysis of the Chinese herb “Flower Man Sang Hung” was positive for levothyroxine. The patient was extubated 11 days after admission and discharged to a rehabilitation centre after 17 days of hospitalization. The Chinese medicine physician was informed of the events. Conclusions: Herbal products can be the source of illness, medication interactions, and contamination. Awareness should be raised among Chinese medicine physicians, allopathic physicians, and their patients. Clinicians should also have a low threshold of suspicion to seek laboratory analysis of suspect substances when the cause of the clinical presentation is unclear.

We report a case of ethcathinone and methylone poisoning with severe clinical toxicity. This is to our knowledge the first case reported in the medical toxicology literature.A 22-year-old woman was brought to the emergency department following several episodes of tonicoclonic seizures, a few hours after ingesting "legal ecstasy". The patient needed intubation for recurrent seizures, and she was found to have severe hyponatremia (120 mmol/L) that was corrected with hypertonic saline. The patient's mental status improved rapidly, and she was extubated the day following her admission. However, she developed prolonged rhabdomyolysis (CK 34.537 U/L) that required a 6-day hospitalisation.The seizures and the hyponatremia may be explained by the MDMA-like characteristics of methylone that may induce inappropriate secretion of antidiuretic hormone mediated via the serotonin system. The combination of methylone and ethcatinone (both acting like serotonin reuptake inhibitors) might have contributed to neurologic manifestations compatible with serotonin toxicity, although our patient never had autonomic instability. Our patient had a prolonged period of rhabdomyolysis which may also be explained by excessive serotonin activity resulting in an increased motor hyperactivity. The public has to be aware of this growing health problem. Clinicians must report future cases of toxicity related to the use of cathinone synthetic derivatives in order to increase our knowledge of these substances.

Purpose Venoarterial extracorporeal membrane oxygenation represents an emerging and recommended option to treat life-threatening cardiotoxicant poisoning. The objective of this cost-effectiveness analysis was to estimate the incremental cost-effectiveness ratio of using venoarterial extracorporeal membrane oxygenation for adults in cardiotoxicant-induced shock or cardiac arrest compared with standard care. Materials and methods Adults in shock or in cardiac arrest secondary to cardiotoxicant poisoning were studied with a lifetime horizon and a societal perspective. Venoarterial extracorporeal membrane oxygenation cost effectiveness was calculated using a decision analysis tree, with the effect of the intervention and the probabilities used in the model taken from an observational study representing the highest level of evidence available. The costs (2013 Canadian dollars, where $1.00 Canadian = $0.9562 US dollars) were documented with interviews, reviews of official provincial documents, or published articles. A series of one-way sensitivity analyses and a probabilistic sensitivity analysis using Monte Carlo simulation were used to evaluate uncertainty in the decision model. Results The cost per life year (LY) gained in the extracorporeal membrane oxygenation group was $145 931/18 LY compared with $88 450/10 LY in the non-extracorporeal membrane oxygenation group. The incremental cost-effectiveness ratio ($7185/LY but $34 311/LY using a more pessimistic approach) was mainly influenced by the probability of survival. The probabilistic sensitivity analysis identified variability in both cost and effectiveness. Conclusion Venoarterial extracorporeal membrane oxygenation may be cost effective in treating cardiotoxicant poisonings.

Background The optimal age to begin CPR training is a matter of debate. This study aims to determine if elementary schoolchildren have the capacity to administer CPR efficiently. Methods This quasi-experimental study took place in a Quebec City school. Eighty-two children 10 to 12 years old received a 6-hour CPR course based on the American Heart Association (AHA) Guidelines. A comparison group of 20 adults who had taken the same CPR course was recruited. After training, participants’ performance was evaluated using a Skillreporter manikin. The primary outcome was depth of compressions. The secondary outcomes were compression rate, insufflation volume and adherence to the CPR sequence. Children’s performance was primarily evaluated based on the 2005 AHA standards and secondarily compared to the adults’ performance. Results Schoolchildren did not reach the lower thresholds for depth (28.1 +/− 5.9 vs 38 mm; one-sided p = 1.0). The volume of the recorded insufflations was sufficient (558.6 +/222.8 vs 500 ml; one-sided p = 0.02), but there were a significant number of unsuccessful insufflation attempts not captured by the Skillreporter. The children reached the minimal threshold for rate (113.9 +/−18.3 vs 90/min; one-sided p

The object of the current communication is to discuss the theory and the evidence for the use of L-carnitine in calcium channel blocker and metformin poisonings.A 68-year-old male known for hypertension and type II diabetes was admitted to the critical care unit of a community hospital following an overdose of amlodipine and metformin. The patient was intubated, ventilated, and hemodynamically supported with vasopressors. Despite calcium, glucagon, high-dose insulin (HDI), and lipid emulsion for calcium channel blocker and bicarbonate for metabolic acidosis, the patient remained hemodynamically unstable. The patient was considered too unstable to initiate continuous renal replacement therapy; and without access to extracorporeal life support, the administration of L-carnitine was administered as a last resort. One hour after L-carnitine, the norepinephrine requirements started to decrease, the patient began to improve and was subsequently extubated successfully without apparent sequelae in less than 4 days.L-Carnitine combined with HDI may have helped with the calcium channel blocker (CCB) poisoning by decreasing insulin resistance, promoting intracellular glucose transport, facilitating the metabolism of free fatty acids, and increasing calcium channel sensitivity. It may have also stimulated oxidative utilization of glucose instead of converting pyruvate into lactate and contributed to decrease lactate production with metformin poisoning.

This article reviews invasive and noninvasive ventilation for emergency physicians. It presents an overview of respiratory physiology principles that will help emergency physicians adapt their ventilation strategies to any clinical situation. The basic modes of ventilation are summarized. The advantages and limitations of certain novel modes of ventilation are presented. This review highlights a variety of ventilation strategies to be used for patients with normal lung mechanics and gas exchange, acute hypoxemic respiratory failure, decreased lung compliance, airflow obstruction, and weakness or restriction of the chest wall. This article will help clinicians prevent, recognize, and treat complications of mechanical ventilation.

A shortcut review was carried out to establish whether silibinin is better than conservative management at reducing liver transplantation and death after poisoning with amatoxin-containing mushrooms. Thirty-eight papers were found in Medline and 86 in EMBASE using the reported searches. Of these, five presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. It is concluded that the evidence is limited, but given the lack of alternative treatments in patients with suspected amatoxin-containing mushroom poisoning and the relatively few adverse effects, silibinin should be considered in some patients.

Background: Covalent binding by reactive drug metabolites represents a poorly understood cause of drug toxicity. Currently, assessing protein covalent binding usually entails the use of radioactive drug and therefore has limited applicability in drug discovery. Several marketed drugs are known to form reactive metabolites and have been shown to covalently bind to proteins. Results: In this article, we describe a new method for the analysis of reactive metabolite–protein binding by MS using a strategy of complete digestion of microsomal proteins into free amino acids. Immobilized pronase was found to be the best method for complete digestion in terms of stability of amino acid modifications as well as minimized spectral background. Conclusion: Modified cysteine residues were identified for four tested drug compounds known to form reactive metabolites following in vitro microsomal incubations and accurate mass measurements by LC–MS analysis.

A 42-yr-old man was admitted to hospital for emergent coronary angioplasty. The patient’s trachea was intubated prior to catheterization and a trial tracheal extubation was attempted four days into his admission; however, the patient was promptly reintubated with a subglottic secretion drainage endotracheal tube after developing severe epistaxis. He had no documented stridor at that time. Nine days into his admission, the patient’s trachea was extubated successfully, and he was transferred to the ward where he experienced a progressive voice change. On day 12, he developed sudden onset stridor and required heliox to maintain oxygenation. He was started on corticosteroids and empiric antibiotics and was admitted to the intensive care unit. The otolaryngologist was consulted to perform fibreoptic laryngoscopy, the results of which revealed normal vocal cords. The patient was sent for computed tomography (CT) (Fig. 1), and those results showed a casting of debris within the upper trachea (a craniocaudal dimension of 27 mm) that narrowed the tracheal airway to 5 mm in diameter. The patient then underwent rigid bronchoscopy. He was sedated initially with sevoflurane for laryngoscopy and then sedated further with fentanyl and ketamine and paralyzed with succinylcholine. A rigid bronchoscope was introduced just above the obstructing lesion. At this point, jet ventilation was inadequate to maintain oxygenation; therefore, the bronchoscope was