Lipid emulsion therapy during management of the critically-ill poisoned patient: a prospective cohort study.

BACKGROUND: Despite conflicting data, intravenous lipid emulsion has emerged as a potential antidote. The "lipid sink" theory suggests that following intravenous administration of lipid, lipophilic drugs are sequestered in the vascular compartment, thereby reducing their tissue concentrations. This study sought to determine if survival is associated with the intoxicant's degree of lipophilicity. METHODS: We reviewed all cases in the Toxicology Investigators Consortium's lipid sub-registry between May 2012 through December 2018. Information collected included demographics, exposure circumstances, clinical course, management, disposition, and outcome. The primary outcome was survival after lipid emulsion therapy. Survival was stratified by the log of the intoxicant's octanol-water partition coefficient. We also assessed the association between intoxicant lipophilicity and an increase in systolic blood pressure after lipid emulsion administration. RESULTS: We identified 134 patients, including 81 (60.4%) females. The median age was 40 years (interquartile range 21-75). One hundred and eight (80.6%) patients survived, including 45 (33.6%) with cardiac arrest during their intoxication. Eighty-two (61.2%) were hypotensive, and 98 (73.1%) received mechanical ventilation. There was no relationship between survival and the log of the partition coefficient of the intoxicant on linear analysis (P = 0.89) or polynomial model (P = 0.10). Systolic blood pressure increased in both groups. The median (interquartile range) systolic blood pressure before lipid administration was 68 (60-78) mmHg for those intoxicants with a log partition coefficient < 3.6 compared with 89 (76-104) mmHg after lipid administration. Among those drugs with a log partition coefficient > 3.6, the median (interquartile range) was 69 (60-84) mmHg before lipid and 89 (80-96) mmHg after lipid administration. CONCLUSION: Most patients in this cohort survived. Lipophilicity was not correlated with survival or the observed changes in blood pressure. The study did not address the efficacy of lipid emulsion.

Utilizing learning communities to deliver an integrated undergraduate medical education curriculum.

AIM: Learning communities (LCs) have been identified as a structure to support student wellness as well as create a positive learning environment and have been increasingly adopted in undergraduate medical education (UGME). In 2016, Michigan State University College of Human Medicine made curricular changes which integrated basic, social, and clinical sciences. One of the major strategies adopted to deliver this integrated curriculum was to create LCs that served as a central scaffold for students' academic development. Our primary aim is to describe how the school utilized LC faculty to deliver this core integrated curriculum. METHODS: Students were surveyed about their perceptions of the effectiveness of the LCs in delivering an integrated science curriculum. Student academic performance in the new curriculum was compared to that of students from the legacy curriculum as a measure of the effectiveness of the curricular changes. RESULTS: The percentage of students in each class who responded to surveys ranged between 78.7% and 95.8%. Mean Likert responses (1 = strongly disagree; 5 = strongly agree) for statements 'the Faculty Fellow is effective in helping me learn the scholar group content', 'the Faculty Fellow is an effective teacher in our scholar group', and 'the Faculty Fellow is well prepared for our scholar group' ranged from 4.37 to 4.78, 4.72 to 4.76, and 4.81 to 4.86, respectively. In addition, a comparison of summative exam scores of the new curriculum's students to the legacy curriculum's students demonstrated comparable or better performances in the new curriculum. CONCLUSIONS: Utilizing LCs to deliver an integrated science curriculum is an underutilized strategy in UGME. Surveys on student satisfaction and academic performance are encouraging. Additional outcome measures are planned to continually evaluate this innovative multifaceted integration.

Accidental Chlorine Gas Exposure in a Pediatric Patient: A Case Report.

INTRODUCTION: Chlorine gas is a known irritant of the respiratory tract, which may cause damage to various systems depending on time of exposure and concentration of the gas. Current treatments are mainly supportive. While no definitive studies have been completed to date, it has been noted that treatment with a sodium bicarbonate solution via nebulizer may lead to improved outcomes for patients dealing with chlorine gas exposure. CASE REPORT: We present a case of a nine-year-old child arriving at the emergency department after exposure to chlorine gas. Complete recovery from his symptoms occurred rapidly with the administration of nebulized sodium bicarbonate. DISCUSSION: Inhaled chlorine gas acts as a mucous membrane irritant, with symptoms usually beginning within minutes of exposure. Inhaled nebulized sodium bicarbonate has been suggested as a therapy for chlorine exposure. Although its mechanism of action is not well understood, it is thought that inhaled sodium bicarbonate neutralizes the hydrochloric acid formed when the chlorine gas reacts with the water in the lungs. CONCLUSION: Nebulized sodium bicarbonate solution at a low concentration appeared to rapidly and effectively reverse the symptoms due to chlorine gas inhalation in a young child.

The Toxicology Investigators Consortium Case Registry-the 2018 Annual Report.

The Toxicology Investigators Consortium (ToxIC) Registry was established by the American College of Medical Toxicology (ACMT) in 2010. The Registry collects data from participating sites with the agreement that all bedside medical toxicology consultation will be entered. The objective of this ninth annual report is to summarize the Registry's 2018 data and activity with its additional 7043 cases. Cases were identified for inclusion in this report by a query of the ToxIC database for any case entered from 1 January to 31 December 2018. Detailed data was collected from these cases and aggregated to provide information which included demographics, reason for medical toxicology evaluation, agent and agent class, clinical signs and symptoms, treatments and antidotes administered, mortality, and whether life support was withdrawn. A total of 51.5% of cases were female, 48% were male, and 0.6% transgender. Non-opioid analgesics were the most commonly reported agent class, followed by antidepressants and opioids. Acetaminophen was once again the most common agent reported. There were 106 fatalities, comprising 1.5% of all registry cases. Major trends in demographics and exposure characteristics remained similar to past years' reports. Sub-analyses were conducted to describe exposures in elderly patients, addiction consultation practices, and risk factors for bupropion-induced seizures. The launch of the ToxIC Qualified Clinical Data Registry (TQCDR) is also described.

BET 2: Low-dose ketamine for acute pain in the ED.

A short cut review was carried out to establish whether low-dose ketamine is better than morphine at safely and effectively reducing pain scores in ED patients with acute pain who do not respond to conventional therapies. One hundred and thirty-two papers were found using the reported searches, of these three 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 that ketamine can be an effective alternative or adjunct to intravenous opioid pain medications and in some instances may provide more effective pain relief when compared with opioids.

Utilization of Observation Units for the Care of Poisoned Patients: Trends from the Toxicology Investigators Consortium Case Registry.

Many poisoned patients may only require a period of observation after their exposure. There are limited data describing the use of observation units for managing poisoned adult and pediatric patients. We performed a retrospective review of all patients reported to the ToxIC Case Registry between January 1, 2012 and December 31, 2013. Eligible patients included those who received a bedside consultation by a medical toxicologist and whose care was provided in an observation unit, or those who were admitted under the care of a medical toxicologist in an observation unit. A total of 15,562 poisonings were reported to the registry during the study period, of which 340 (2.2 %) involved patients who were cared for in an observation unit. Of these patients, 22.1 % were 18 years of age or younger, and the remaining 77.9 % were greater than 18 years of age. The most common reason for exposure was the intentional ingestion of a pharmaceutical agent in both adult (30.2 %) and pediatric patients (36.0 %). Alcohols (ethanol) (24.9 %), opioids (20.0 %), and sedative-hypnotics (17.7 %) were the most common agent classes involved in adult patient exposures. The most common agent classes involved in pediatric exposures were antidepressants (12.0 %), anticonvulsants (10.7 %), and envenomations (10.7 %). In adult patients, the most common signs and symptoms involved the nervous system (52.0 %), a toxidrome (17.0 %), or a major vital sign abnormality (14.7 %). In pediatric patients, the most common signs and symptoms involved the nervous system (53.3 %), a toxidrome (21.3 %), or a major vital sign abnormality (17.3 %). The results of this study demonstrate that a wide variety of poisoned patients have been cared for in an observation unit in consultation with a board-certified medical toxicologist. Patterns for the reasons for exposure, agents responsible for the exposure, and toxicological treatments will continue to evolve. Further study is needed to identify better those poisoned patients who can be appropriately managed in an observation unit.

Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. BET 1: use of a procalcitonin algorithm to guide antimicrobial therapy in COPD exacerbations can reduce antibiotic consumption with no increase in rates of treatment failure or mortality.

A shortcut review was carried out to establish whether a procalcitonin-guided algorithm could safely reduce antibiotic consumption for patients with an exacerbation of chronic obstructive pulmonary disease attending the emergency department. Four randomised controlled trials were found directly relevant to the three-part question, combined within a later systematic review and meta-analysis. A further prospective cohort study was also found relevant to the three-part question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. The clinical bottom line is that a procalcitonin algorithm appears to be a useful strategy to guide initiation and duration of antibiotics and can reduce consumption without conferring additional risk. However, no cost effectiveness data are available as yet and further validation studies are required prior to widespread recommendation.

Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. BET 2: Is shift work bad for you?

A shortcut review was carried out to establish whether night shift working worsens health and shortens life. 127 papers were found using the reported searches, of which one systematic review 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 this paper are tabulated. It is concluded that shift work is associated with an increased risk of vascular events but does not appear to have an effect on mortality.

Hypoglycemia after accidental pediatric sulfonylurea ingestions.

BACKGROUND: Because the prevalence of type 2 diabetes increases annually, there has been an increase in pediatric exposures to sulfonylureas. These medications are associated with delayed and often prolonged hypoglycemia. As such, most authorities but not all recommend admission for all pediatric patients with an accidental sulfonylurea ingestion. METHODS: This study is a retrospective chart review of all pediatric patients with sulfonylurea exposures admitted for 9 years at an urban, pediatric teaching hospital. The incidence and characteristics of the hypoglycemia were recorded and analyzed. RESULTS: During this time span, 93 patients with accidental sulfonylurea exposures were admitted, with a median age of 1.83 years. Glyburide and glipizide accounted for most sulfonylureas. Hypoglycemia (blood glucose level <50 mg/dL) developed in 25 (58.1%) of 43 patients who ingested glipizide, compared with 10 (25.6%) of 39 patients who ingested glyburide. The overall incidence of hypoglycemia was 44%. Hypoglycemia was more likely to occur with glipizide ingestion than glyburide (odds ratio, 3.89 [95% confidence interval, 1.51-9.98]). No patient with a known time of ingestion developed hypoglycemia after 13 hours. CONCLUSIONS: Hypoglycemia is common after accidental sulfonylurea exposures. The results of this study support mandatory admission to a monitored setting for at least 16 hours, with frequent glucose determinations.

Late hematologic toxicity following treatment of rattlesnake envenomation with crotalidae polyvalent immune Fab antivenom.

BACKGROUND: North American rattlesnake envenomations commonly produce defibrination, coagulopathy and/or thrombocytopenia, which may be reversed following treatment with Crotalidae Polyvalent Immune Fab Ovine (FabAV). Despite initial resolution with FabAV, late onset or recurrence of venom-induced hematologic effects may occur. Time at which onset of late hematotoxicity may first be detected is unknown. The purpose of this study was to identify the incidence and time of onset of recurrent or new late hypofibrinogenemia, coagulopathy, or thrombocytopenia in a cohort of rattlesnake envenomation patients seen in outpatient follow-up after treatment with FabAV, and to report hematologic outcomes in these patients. METHODS: Review of 66 charts of patients with rattlesnake envenomation who were treated with FabAV, and subsequently had outpatient follow-up evaluation at least 48 h after last FabAV, was performed. Demographic information, rattlesnake and bite characteristics, dose and timing of antivenom administration, adverse events, in-patient laboratory values, length of hospital stay, and follow-up laboratory values were collected. The primary outcome parameters were recurrent or delayed onset coagulopathy, hypofibrinogenemia, or thrombocytopenia identified no sooner than 48 h after last dose of FabAV. RESULTS: Prior to control of the envenomation with FabAV, 42 patients (63.6%) experienced hematologic toxicity. At follow-up, 21 patients (32%) were found to have late coagulopathy, hypofibrinogenemia, or thrombocytopenia. Of twenty-three patients (35%) with more than one follow-up visit, fifteen had normal laboratory findings at the first follow-up visit. Five of these 15 patients (8% of total study group; 33% of this subgroup) with normal hematologic studies at first follow-up exhibited late hematologic toxicity at second follow-up. Severe late hematologic toxicity developed in five of 66 (8%) patients. One patient was retreated with FabAV for late severe thrombocytopenia. CONCLUSION: Recurrent and delayed onset of hematologic toxicity in rattlesnake envenomation victims treated with FabAV is common. Follow-up more than three days after treatment is necessary to detect all cases of late hematologic toxicity.

Outcomes after isolated mirtazapine (Remeron) supratherapeutic ingestions.

Mirtazapine (Remeron) is a newly approved medication for the treatment of depression. It is an alpha(2)-adrenergic antagonist that causes increased levels of neuronal norepinephrine and serotonin. It is also believed to be an antagonist at the serotonin receptors 5-HT(2) and 5-HT(3). Little is known about isolated mirtazapine ingestions. We conducted a retrospective chart review of mirtazapine ingestions reported to our Poison Center during 2004. A standardized data sheet was completed collecting information regarding standard demographic data along with co-ingestants, neurologic and cardiovascular symptoms, and disposition. Data collection was reviewed by a second investigator, and a kappa score was calculated. Of 71 patients identified with mirtazapine ingestions, there were 33 isolated exposures that were further reviewed. A kappa score for inter-reviewer reliability was calculated and at 0.61, 95% confidence interval 56-70. The average age of these patients was 27 years (range 6-82 years), with the mean ingestion of 343 mg (range 15-1500 mg). The most common neurologic symptom was drowsiness seen in 8/23 patients, 1 patient became agitated, and 14 patients had no abnormal neurologic findings. Cardiovascular effects were recorded in 4/23 patients, with 3 patients exhibiting tachycardia and 1 patient with bradycardia and hypotension. Seven of 23 patients required admission; there were no deaths. Mirtazapine overdoses are generally very well tolerated, with the most common symptoms being drowsiness and lethargy. This study is limited by being a retrospective chart review.

Onset of symptoms after methadone overdose.

BACKGROUND: Methadone ingestion may cause delayed coma and require naloxone infusion. Few studies exist regarding the time development of symptoms following methadone overdose in adults. METHODS: After a brief training period, reviewers who were blinded to the purpose of the study completed a standardized data collection sheet. Two consecutive years of poison center patient encounters were reviewed. Age, outcomes, coingestions, vital signs, clinical manifestations, hospital admissions, and mortality were abstracted. Data were analyzed using descriptive statistics. The first reviewer was designated to extract the data. The second reviewer conducted a review of 20% of all the charts for a kappa value to be calculated. RESULTS: In total, 44 cases of isolated methadone overdose in patients older than 18 years were identified. A mean age of 32.5 (18-58) years and a mean presumed ingestion of 106 mg of methadone was calculated. Of the 44 patients, 32 received naloxone for symptoms consistent with opiate toxicity. All symptoms occurred within 9 hours of methadone ingestion, with a mean symptom onset of 3.2 hours. All patients had resolution of symptoms within 24 hours. No deaths were recorded. The kappa score for interreviewer reliability was 0.69, with a 95% confidence interval of 0.58 to 0.73. LIMITATIONS: This was a retrospective study that was limited by patient history. CONCLUSION: Acute methadone toxicity typically results in symptoms within 9 hours of ingestion.