High lethality and minimal variation after acute self-poisoning with carbamate insecticides in Sri Lanka – implications for global suicide prevention

Background: Highly hazardous organophosphorus (OP) insecticides are responsible for most pesticide poisoning deaths. As they are removed from agricultural practice, they are often replaced by carbamate insecticides of perceived lower toxicity. However, relatively little is known about poisoning with these insecticides.

Methods: We prospectively studied 1288 patients self-poisoned with carbamate insecticides admitted to six Sri Lankan hospitals. Clinical outcomes were recorded for each patient and plasma carbamate concentration measured in a sample to confirm the carbamate ingested.

Findings: Patients had ingested 3% carbofuran powder (719), carbosulfan EC25 liquid (25% w/v, 389), or fenobucarb EC50 liquid (50% w/v, 127) formulations, carbamate insecticides of WHO Toxicity Classes Ib, II, and II, respectively. Intubation and ventilation was required for 183 (14.2%) patients while 71 (5.5%) died. Compared with carbofuran, poisoning with carbosulfan or fenobucarb was associated with significantly higher risk of death [carbofuran 2.2%; carbosulfan 11.1%, OR 5.5 (95% CI 3.0–9.8); fenobucarb 6.3%, OR 3.0 (1.2–7.1)] and intubation [carbofuran 6.1%; carbosulfan 27.0%, OR 5.7 (3.9–8.3); fenobucarb 18.9%, OR 3.6 (2.1–6.1)]. The clinical presentation and cause of death did not differ markedly between carbamates. Median time to death was similar: carbofuran 42.3?h (IQR 5.5–67.3), carbosulfan 21.3?h (11.5–71.3), and fenobucarb 25.3?h (17.3–72.1) (p?=?0.99); no patients showed delayed onset of toxicity akin to the intermediate syndrome seen after OP insecticide poisoning. For survivors, median duration of intubation was 67.8?h (IQR 27.5–118.8) with no difference in duration between carbamates. Reduced GCS at presentation was associated with worse outcome although some patients with carbosulfan died after presentation with normal GCS.

Conclusions: We did not find carbamate insecticide self-poisoning to vary markedly according to the carbamate ingested although the case fatality varied according to the concentration and formulation of the insecticide. Carbamate poisoning did not appear to be much less toxic than poisoning with some liquid OP insecticide formulations, e.g., chlorpyrifos EC40, that we have previously noted in these same hospitals (Lancet 2005, 366:1452–1459; QJM 2006, 99:513–522). Replacement of WHO Class II Toxicity OP insecticides in agriculture with high-strength liquid carbamate formulations may not substantially reduce case fatality after pesticide poisoning and, therefore, global suicide rates.     

Serum S100 protein could predict altered consciousness in glyphosate or glufosinate poisoning patients

Background: Central nervous system (CNS) complications such as seizures and reduced consciousness are important in glufosinate and may occur in severe glyphosate poisoning. The aim of this study was to assess the possible role of serum S100B protein as a biochemical marker of CNS complications associated with glyphosate or glufosinate poisoning.

Methods: The study enrolled 40 patients (23 glyphosate poisoning and 17 glufosinate poisoning). Altered consciousness and seizure were observed during hospitalization. S100B level was measured with fully automated modular analytic E170 system using electrochemoluminometric immunoassay.

Results: Among 40 patients, neurologic features were observed in 12 patients with a median time to onset of 21.5 (IQR 8.25–24.75) h. Serum S100B concentrations measured on admission were higher in the group with neurologic features than in the group without neurologic features [0.148?μg/L (IQR 0.128–0.248) vs. 0.072?μg/L (IQR 0.047–0.084), p?Conclusions: In our pilot study, S100B was a significant predictor of neurologic complications in patients with glyphosate and glufosinate poisoning. Large prospective cohorts are needed to confirm this finding.     

Relative Toxicity of Selective Serotonin Reuptake Inhibitors (SSRIs) in Overdose

Background: Selective serotonin reuptake inhibitors (SSRIs) have increasingly replaced tricyclic antidepressants (TCAs) in the treatment of depression. They appear to be safer in overdose, but there is little information on their spectrum of toxicity in overdose, or relative toxicity of each agent. Objective: To determine the effect of SSRIs in overdose, as a group, and the relative toxicity of five different SSRIs. Methods: A review of consecutive SSRI poisoning admissions to a single toxicology unit. Outcomes examined were length of stay [LOS], intensive care [ICU] admission rate, coma, seizures, electrocardiographic [ECG] abnormalities, and presence of serotonin syndrome [SS]. Logistic regression was used to model the outcome QTc > 440 msec. Results: There were 469 SSRI poisoning admissions analyzed after exclusions. The median LOS for all SSRI overdose admissions was 15.3 h (IQR: 10.5–21.3) and 30 of 469 (6.4%; 95% CI 4.3–9.0%) cases were admitted to ICU. The incidence of seizures was 1.9% and coma was 2.4%. Serotonin syndrome occurred in 14% of overdoses. Comparison of median QTc intervals of the five SSRIs was significantly different (p = 0.0002); citalopram (450 IQR: 436–484) was individually different to fluoxetine (p = 0.045), fluvoxamine (p = 0.022), paroxetine (p = 0.0002), and sertraline (p = 0.001). The proportion of citalopram overdoses with a QTc > 440 msec was 68%, differing significantly from sertraline (adjusted OR: 5.11 95% CI 2.32–11.27). Comparison of median QT intervals of the five SSRIs was statistically different (p = 0.026); citalopram (400 IQR: 380–440) was individually different from sertraline (p = 0.023). Conclusions: This study shows SSRIs are relatively safe in overdose despite serotonin syndrome being common. The exception was citalopram, which was significantly associated with QTc prolongation. We believe that cardiac monitoring should be considered in citalopram overdose, particularly with large ingestions and patients with associated cardiac disease.     

Organophosphate-pyrethroid combination pesticides may be associated with increased toxicity in human poisoning compared to either pesticide alone

Background. Organophosphate (OP) poisoning results in significant toxicity while pyrethroid poisoning is associated with extremely low fatality. OPs can inhibit the detoxification of pyrethroid and increase the toxicity of the combination. We assessed whether mixed OP-pyrethroid poisoning impacted outcome in human poisoning. Methods. Patients were identified from a prospectively collected institutional poisoning database that incorporates demographic and outcome data of patients presenting with poisoning. Results. Of the 1177 poisoned patients admitted over 2 years, 32 presented with OP-pyrethroid (50% chlorpyrifos-5% cypermethrin mixture) poisoning (Group 1), 26 consumed 20% chlorpyrifos (Group 2), and 32 took 15% cypermethrin (Group 3). Seizures occurred in 15.6% (n = 5) with chlorpyrifos-cypermethrin poisoning, 18.8% (n = 6) with cypermethrin poisoning, and 3.9% (n = 1) with chlorpyrifos poisoning. Ventilatory requirements were 53.5% (17/32), 42.3% (11/26), and 15.7% (5/32) in Groups 1–3, respectively. Ventilator-free days (Mean ± SD) was significantly lower (p < 0.006) in Group 1 (20.9 ± 9.3 days) than those in Group 2 (26.1 ± 4.4 days) or 3 (27.8 ± 0.6). The median (inter-quartile range) hospital stay was 5.5 (4–19.5), 5 (5–6), and 1 (0.65–1.5) days, respectively, in the three groups. Four patients died in Group 1 (13%). None died in the other groups. Conclusion. Although confounded by the varying quantity of chlorpyrifos and cypermethrin in the different formulations, patients with mixed poisoning appear to have shorter ventilator-free days than patients poisoned by either of the pesticides alone. Further studies are required comparing patients poisoned by formulations with similar quantities of OP and pyrethroid or with analysis of blood pesticide concentration on admission.     

Development of renal function during staged balloon pulmonary angioplasty for inoperable chronic thromboembolic pulmonary hypertension

Balloon pulmonary angioplasty (BPA), for chronic thromboembolic pulmonary hypertension, improves pulmonary and systemic hemodynamics. The kidney might benefit from this effect. However, staged BPA therapy comes along with repetitive administration of contrast agent. This study examined the overall effect of BPA therapy on renal function. This study included consecutive patients who underwent BPA treatment and completed a 6-month follow-up between March 2014 and March 2017. Biomarker-based evaluation of renal function was performed at baseline, consecutively prior to and after each BPA and at 6-month follow-up. The 51 patients underwent an average of 5 (±2) BPA sessions. In this course, patients received 133 (±48; 21–300) mL of contrast agent per session and 691 (±24; 240–1410) mL during the whole sequence. Acute kidney injury occurred after 6 (2.3%) procedures. The creatinine [80.1 (IQR 67.8–96.8) µmol/L vs. 77.4 (IQR 66.9–91.5) µmol/L, p?=?.02] and urea level [13.7 (IQR10.7–16.6) mmol/L vs. 12.5 (IQR 10.0–15.5) mmol/L, p?=?.02] decreased from baseline to the 6-month follow-up. The estimated glomerular filtration rate (eGFR) [79 (IQR 59–94) mL/min/m² vs. 79.6 (IQR 67.1–95.0) mL/min/m², p?=?.11] did not change. The Chronic kidney disease (CKD) stages at baseline were: G1:15; G2:23; G3a:10; G3b:2; G4:1; G5:0. Among patients with a CKD-stage ≥2, analysis revealed an increase of eGFR, decrease of creatinine and urea from baseline to 6-month follow-up. Among those patients, the baseline-CKD-stage improved in 14 (41.2%) patients. BPA therapy improves pulmonary and systemic hemodynamics, with positive effects on renal function. Repetitive administration of contrast agent seems not to be harmful regarding renal function.     

Short-term glucose dysregulation following acute poisoning with organophosphorus insecticides but not herbicides,carbamate or pyrethroid insecticides in South Asia

Background: Ingestion of organophosphorus (OP) insecticides is associated with acute hyperglycaemia. We conducted a prospective study to determine whether glucose dysregulation on admission associated with ingestion of OP insecticides or other pesticides is sustained to hospital discharge or to 3–12 months later.

Methods: We recruited participants to two similar studies performed in parallel in Anuradhapura, Sri Lanka, and Chittagong, Bangladesh, following hospitalisation for OP insecticide, herbicide or other pesticide self-poisoning. Two-hour 75?g oral glucose tolerance testing (OGTT) was performed after recovery from the acute poisoning, at around the time of discharge. In Sri Lanka, a four time-point OGTT for area-under-the-curve (AUC), C-peptide and homeostatic modelling of insulin resistance (HOMA-IR) was undertaken, repeated after 1 year. In Bangladesh, a 2-h OGTT for glucose was undertaken and repeated after 3 months in participants with initial elevated 2-h glucose. We compared glucose homeostasis by poison group and adjusted findings for age, BMI and sex.

Findings: Seventy-three Sri Lankan and 151 Bangladeshi participants were recruited. We observed higher mean [SD] fasting (4.91 [0.74] vs. 4.66 [0.46] mmol/L, p?=?.003) and 2-h glucose (7.94 [2.54] vs. 6.71 [1.90] mmol/L, p?p?=?.352; 2-h glucose 6.96 [2.31] mmol/L vs. 6.27 [1.86] mmol/L, p?=?.225).

Conclusion: We found in this small prospective study that acute OP insecticide poisoning caused acute glucose dysregulation that was sustained to hospital discharge but had recovered by 3–12 months. Acute glucose dysregulation was related to defects in insulin action and secretion. This study did not address long-term risk of diabetes following acute OP insecticide poisoning, but could provide the data for a power calculation for such a study     

Clinical outcomes from early use of digoxin-specific antibodies versus observation in chronic digoxin poisoning (ATOM-4)

Introduction: In our previous study on chronic digoxin poisoning, there was a minor improvement after treatment with digoxin-specific antibody (digoxin-Fab). We hypothesised patients with elevated digoxin concentrations may derive little benefit from digoxin-Fab because their presenting complaint was more closely related to their multiple co-morbidities. We aimed to compare the outcome of patients who were initially treated with digoxin-Fab with those that received supportive care.

Method: Patients were prospectively recruited to the study if they had an elevated digoxin concentration, signs or symptoms of toxicity thought to be from digoxin. Patients who were initially managed with digoxin-Fab were compared with those not initially receiving digoxin-Fab (observation group). Patients presented with ventricular arrhythmias before initial assessment were excluded from the analysis. Primary outcome was mortality. Secondary outcomes were length of stay (LOS), change in heart rate (HR) and potassium concentration.

Results: From September 2013 to January 2018, 128 patients were recruited of which 78 (61%) received initial digoxin-Fab. Digoxin-Fab and supportive care groups had an initial median heart rate of 46 (range: 20–120) vs 52 bpm (range: 29–91) (p?=?.06), systolic blood pressure of 110?mmHg (range: 65–180) vs 125?mmHg (range: 90–184) (p?=?.009), respectively. Digoxin concentrations 4.4?nmol/L (range: 3.3–9) vs 4.2 (range: 2–11.2) (p?=?.42) and potassium concentrations 5.4?mmol/L (range: 3–11) vs 5.1?mmol/L (range: 3.5–8.2) (p?=?.33) were similar. Median dose of digoxin-Fab used was 1.5 vials (IQR: 1–2). There were 9 (12%) deaths in the Fab group compared to 7 (14%) in those treated with supportive care (risk difference ?2.5%; 95% CI: ?14 to 9%; p?=?.68). The median LOS was six days in both groups. Mean changes in potassium concentration [?0.5?±?0.1 vs. ?0.4?±?0.1?mmol/L; difference ?0.1 (95% CI: ?.02, 0.4), p?=?.70] and HR within 4?h [8?±?1 vs. 7?±?3 bpm; difference ?1.0 (95% CI: ?6.7, 4.8), p?=?0.74] were similar in the two groups.

Conclusions: This study did not appear to show any benefit from the routine use of digoxin-Fab in patients thought to have chronic digoxin poisoning. These patients have multiple co-morbidities that may be contributing to their clinical features, other treatments are often equally effective.     

The effect of the severity COVID-19 infection on electrocardiography

ObjectiveAcute myocardial damage is detected in a significant portion of patients with coronavirus 2019 disease (COVID-19) infection, with a reported prevalence of 7–28%. The aim of this study was to investigate the relationship between electrocardiographic findings and the indicators of the severity of COVID-19 detected on electrocardiography (ECG).MethodsA total of 219 patients that were hospitalized due to COVID-19 between April 15 and May 5, 2020 were enrolled in this study. Patients were divided into two groups according to the severity of COVID-19 infection: severe (n = 95) and non-severe (n = 124). ECG findings at the time of admission were recorded for each patient. Clinical characteristics and laboratory findings were retrieved from electronic medical records.ResultsMean age was 65.2 ± 13.8 years in the severe group and was 57.9 ± 16.0 years in the non-severe group. ST depression (28% vs. 14%), T-wave inversion (29% vs. 16%), ST-T changes (36% vs. 21%), and the presence of fragmented QRS (fQRS) (17% vs. 7%) were more frequent in the severe group compared to the non-severe group. Multivariate analysis revealed that hypertension (odds ratio [OR]: 2.42, 95% confidence interval [CI]:1.03–5.67; p = 0.041), the severity of COVID-19 infection (OR: 1.87, 95% CI: 1.09–2.65; p = 0.026), presence of cardiac injury (OR: 3.32, 95% CI: 1.45–7.60; p = 0.004), and d-dimer (OR: 3.60, 95% CI: 1.29–10.06; p = 0.014) were independent predictors of ST-T changes on ECG.ConclusionST depression, T-wave inversion, ST-T changes, and the presence of fQRS on admission ECG are closely associated with the severity of COVID-19 infection.     

Mirtazapine overdose is unlikely to cause major toxicity

Objective. There is limited information on mirtazapine overdose, but cases of severe effects (seizures, serotonin toxicity and coma) have been reported. We aimed to investigate the clinical effects and complications of mirtazapine overdose. Methods. This was an observational case series of mirtazapine overdoses (> 120 mg) identified from admissions to a toxicology unit between January 1987 and August 2013. Demographic information, details of ingestion, clinical effects, ECG parameters (HR, QT and QRS), and length of stay were extracted from a clinical database. Results. From 267 mirtazapine overdoses, there were 89 single-agent mirtazapine ingestions and 178 cases where mirtazapine was taken with at least one other drug. The median age of the 89 single-agent mirtazapine ingestions was 36 years [interquartile range (IQR): 26–49 years; Range: 15–81 years]; 45 were female (51%). The median ingested dose was 420 mg (IQR: 270–750 mg; Range: 150–1350 mg) and 41 patients (46%) had a Glasgow coma score (GCS) < 15, but the minimum GCS was 10. There were no seizures, serotonin toxicity or delirium. Tachycardia occurred in 29 patients (33%) and hypertension in 32 patients (36%). The median QRS was 80 ms (Range: 80–120 ms) and there were no cases with QT prolongation. There were no arrhythmias and no deaths. The median length of stay was 14 h (IQR: 8.8–18.2 h; Range:2.2–75 h). No single-agent mirtazapine patient was admitted to intensive care. The 178 patients taking co-ingestants had more severe toxicity depending on the co-ingested drug. Conclusion. Mirtazapine appears to be relatively benign in overdose, associated with tachycardia, mild hypertension and mild CNS depression not requiring intervention.     

Circulating cardiac troponin I in trauma patients without cardiac contusion

Objectives: To describe the evolution and the diagnostic value of cardiac troponin I (cTnI) and to relate its concentrations with the indicators of injury in trauma patients. Design: Prospective, observational study of 17 young, previously healthy, mechanically-ventilated patients during the early post-traumatic period in the Surgical ICU of a University Hospital. Methods: Serial measurements of serum cTnI, total creatine kinase activity (CKtot) and its isoenzyme MB (CK-MB) (on admission, 12 h later, then daily for 7 days), clinical data and repeated electrocardiographic (ECG) and transesophageal echocardiographic (TEE) recordings. Results: Rhabdomyolysis was observed in all the patients with a significant relationship between CK-MB and CKtot. Despite the fact that no patient demonstrated ECG or TEE signs of myocardial contusion, elevated serum levels of cTnI were observed in six patients (35 %) without obvious dilutional interference. As compared with the others, these patients exhibited a more frequent arterial hypotension (83 % vs 18 %, p = 0.035), required greater volume expansion on day 1 (22,000 vs 8,500 ml, p = 0.027) and usually demonstrated early (83 % vs 9 %, p = 0.005) and late (66 % vs 9 %, p = 0.028) multiple organ dysfunction syndrome. Conclusions: Taking into account the high reported sensitivity and specificity of cTnI dosage, the present results suggest cTnI can play a role in the evaluation of indirect myocardial injury following traumatic shock. Received: 20 November 1997 Accepted: 3 March 1998     

Salbutamol in acute organophosphorus insecticide poisoning – a pilotdose-response phase II study

Background: Treatment of acute organophosphorus (OP) insecticide poisoning is difficult, with many patients dying despite best care. Pre-clinical studies have shown benefit from salbutamol, possibly due speeding alveolar fluid clearance or reducing bronchoconstriction. In this small pilot dose-response study, we aimed to explore whether addition of nebulized salbutamol to standard care might improve resuscitation.

Methods: We performed a single-blind phase II study comparing the effect of two different doses of nebulized salbutamol versus saline placebo, in addition to standard treatment. Primary outcome was oxygen saturations over the first 60?min of resuscitation; secondary outcomes included heart rate, incidence of dysrhythmias, time to ‘atropinization’, atropine dose required, and mortality.

Result: Seventy-five patients were randomized to receive 5?mg (Salb5, n?=?25) or 2.5mg (Salb2.5, n?=?25) of salbutamol, or saline placebo (NoSalb, n?=?25), by nebulizer. Oxygen saturations did not differ between groups over the first 60?min of resuscitation (median AUC NoSalb: 1376 [95% CI 1282 to 1470], Salb2.5: 1395 [1305 to 1486], Salb5: 1233 [1100 to 1367]; p?=?.9898). Heart rate was also similar across the three arms. Median time to full atropinization, and atropine dose required, were the same for all three arms (NoSalb 15.0 [10–16] min and 12.6 [8.0–13.4] mg, Salb2.5 15.0 [10–16] min and 12.6 [9.3–16.8] mg, and Salb5 15.0 [10–20] min and 12.6 [10.7–20.6] mg; p?=?.4805 and p?=?.1871, respectively). Three (12%) patients died in the Salb2.5 and Salb5 groups and two (8%) in the NoSalb group.

Conclusion: This pilot study, within the limitations of its small size and variation between patients, found no apparent evidence that administration of nebulized salbutamol improved resuscitation of patients with acute OP insecticide self-poisoning. The data obtained provides a basis to design further studies to ultimately test the role of salbutamol in OP insecticide poisoning.     

Comparing the Timeliness of Treatment in Younger vs. Older Patients with ST-Segment Elevation Myocardial Infarction: A Multi-Center Cohort Study

BackgroundST-segment elevation myocardial infarction (STEMI) predominantly affects older adults. Lower incidence among younger patients may challenge diagnosis.ObjectivesWe hypothesize that among patients ≤ 50 years old, emergent percutaneous coronary intervention (PCI) for STEMI is delayed when compared with patients aged > 50 years.MethodsThis 3-year, 10-center retrospective cohort study included emergency department (ED) STEMI patients ≥ 18 years of age treated with emergent PCI. We excluded patients with an electrocardiogram (ECG) completed prior to ED arrival or a nondiagnostic initial ECG. Our primary outcome was door-to-balloon (D2B) time. We compared characteristics and outcomes among younger vs. older STEMI patients, and among age subgroups.ResultsThere were 576 ED STEMI PCI patients, of whom 100 were ≤ 50 years old and 476 were > 50 years old. Median age was 44 years in the younger cohort (interquartile range [IQR] 41–47) vs. 62 years (IQR 57–70) among older patients. Median D2B time for the younger cohort was 76.5 min (IQR 67.5–102.5) vs. 81.0 min (IQR 65.0–105.5) in the older cohort (p = 0.91). This outcome did not change when ages 40 or 45 years were used to demarcate younger vs. older. The younger cohort had a higher prevalence of nonwhite races (38% vs. 21%; p < 0.001) and those currently smoking (36% vs. 23%; p = 0.005). The very young (≤30 years; 6/576) and very old (>80 years; 45/576) had 5.51 and 2.2 greater odds of delays.ConclusionWe found no statistically significant difference in D2B times between patients ≤ 50 years old and those > 50 years old. Nonwhite patients and those who smoke were disproportionately represented within the younger population. The very young and very old had higher odds of D2B times > 90 min.     

Do-not-attempt resuscitation independently predict in-hospital mortality in septic patients

IntroductionSepsis patients require timely and appropriate treatment in an intensive care setting. However, “do-not-attempt resuscitation” (DNAR) status may affect physicians' priorities and treatment preferences. The aim of this study was to evaluate whether DNAR status affects the outcomes of septic patients.MethodsThis was a retrospective cohort study included septic patients admitted to the emergency department intensive care unit (ED-ICU) in a university-based teaching hospital during April–November 2015. Septic patients admitted to the ED-ICU were included.ResultsOf the 132 eligible patients, 49.2% (65/132) had DNAR status (median age 80 years old, IQR, 73–86). The overall in-hospital mortality rate was 28.8% (38/132). Non-survivors had a higher percentage of receiving inotropes/vasopressors (52.6% vs 34.0%, p = 0.048), higher median Charlson comorbidity index scores [8.5 (IQR, 7–11.75) vs 8 (IQR, 6–9), p = 0.012], higher APACHE II score [25 (IQR, 20–30.25) vs 20 (IQR, 17–25), p = 0.002], and higher SOFA score [7 (IQR, 6–11) vs 6 (IQR,4–8), p = 0.012]. There was no significant difference in intubation among the two groups. In a multivariate logistic regression analysis, DNAR status was an independent predictor of in-hospital mortality (odds ratio = 6.22, 95% confidence interval (CI) = (2.71–17.88), p < 0.001). The area under the ROC curve for the logistic regression model was 0.84 [95% CI = (0.77–0.92), p < 0.001]. In subgroup analysis, DNAR status remained an independent predictor of mortality among age ≥65 years and ≥80 years.ConclusionAfter adjusting for comorbidities, treatments, and illness severity, DNAR status was associated with in-hospital mortality of septic patients. Further studies should evaluate physicians' attitudes toward septic patients with DNAR status.     

Extrapyramidal effects of acute organophosphate poisoning

Background: There is limited information on extrapyramidal symptoms in acute organophosphate (OP) poisoning. We describe the course and outcome of severely poisoned patients who develop extrapyramidal manifestations. Methods: In this prospective observational study, spanning 8 months (Apr–Nov 2013) adult patients (>18 years) admitted with OP poisoning were enrolled. Patients on anti-psychotic therapy, those refusing consent or presenting with co-ingestions were excluded. Treatment included atropine and supportive care (e.g. ventilation and inotropes as indicated); oximes were not administered. The presence of rigidity, tremors, dystonia and chorea were assessed daily till discharge using modifications of the Unified Parkinson’s Disease rating scale and the Tremor rating scale. The presence of extrapyramidal manifestations was correlated with length of ventilation and hospital stay and mortality. Results: Of the 77 patients admitted with OP poisoning, 32 were enrolled; 17 (53.1%) developed extrapyramidal manifestations which included rigidity (94.1%), tremors (58.8%) and dystonia (58.8%). None developed chorea. The median (inter-quartile range) time of symptom onset was 8 (5–11) days; extrapyramidal features resolved in 11 (6–17) days. The median duration of intensive care stay in patients not developing extrapyramidal symptoms was 6 (2–8) days, indicating that most of these patients had recovered even before symptom onset in patients who developed extrapyramidal manifestations. Overall, 27/32 (84%) were ventilated. Hospital mortality was 6.25% (2/32). When compared with patients not developing extrapyramidal signs, those with extrapyramidal manifestations had significantly prolonged ventilation (5 versus 16 median days; p?=?0.001) and hospitalization (8 versus 21 days; p?<?0.001), reduced ventilator-free days (23 versus 12 days; p?=?0.023) and increased infections (p?=?0.03). The need for ventilation and mortality were not significantly different (p?>?0.6). Extrapyramidal symptoms were not observed in non-OP poisoned patients with prolonged ICU stay. Conclusion: In this small series of acute OP poisoning, extrapyramidal manifestations were common after 1 week of intensive care but self-limiting. They are significantly associated with longer duration of ventilation and hospital stay.     

Lithium poisoning in the intensive care unit: predictive factors of severity and indications for extracorporeal toxin removal to improve outcome

Context: Lithium is responsible for life-threatening poisoning, not consistently improved by extracorporeal toxin removal (ECTR).

Objective: Our aim was to identify predictive factors on admission of poisoning severity and based on an evaluation of practice, report indications for ECTR susceptible to improve outcome

Methods: We performed a retrospective cohort study including all lithium-poisoned patients admitted to the ICU in a university hospital. The usual clinical, biological and toxicological variables were collected. Poisoning severity was defined by seizures, catecholamine infusion, mechanical ventilation >48?h and/or fatality. Univariate followed by multiple logistic regression analyses were performed to identify prognosticators of poisoning severity and ECTR use.

Results: From 1992 to 2013, 128 lithium-poisoned patients including acutely (10%), acute-on-chronically (63%) and chronically poisoned patients (27%) were included. The presumed ingested dose of lithium was 17.0?g [8.0–24.5] (median [25th–75th percentiles]). Serum lithium concentrations were 2.6?mmol/l [1.5–4.6], 2.8?mmol/l [1.8–4.5] and 2.8?mmol/l [2.1–3.0] on admission, peaking at 3.6?mmol/l [2.6; 6.2], 4.3?mmol/l [2.4; 6.2] and 2.8?mmol/l [2.1; 3.1] in the three groups, respectively. Severe poisoning occurred in 48 patients (38%) including four fatalities. Using the regression analysis, predictive factors of poisoning severity were Glasgow coma score ≤10 (Odds ratio (OR), 11.1; 95% confidence interval (CI), [4.1–33.3], p?p?=?0.005). Ninety-eight patients (77%) developed acute kidney injury according to KDIGO criteria and 22 (17%) were treated with ECTR. Peak lithium concentration ≥5.2?mmol/l (OR, 22.4; CI, [6.4–96.4]; p?p?=?0.01) were associated with ECTR use. Only 21/46 patients who presented one of these two criteria were actually treated with ECTR. More significant neurological impairment persisted on discharge in patients not treated with ECTR (p?=?0.0007) despite not significantly shorter length of ICU stay.

Conclusions: Lithium poisoning is responsible for severe impairments but rare fatalities. Severity can be predicted on admission using Glasgow coma score and lithium concentration. Our results suggest that ECTR could be indicated if serum lithium ≥5.2?mmol/l or creatinine ≥200?μmol/l.     

Early recognition of sepsis through emergency medical services pre-hospital screening

BackgroundThe Surviving Sepsis Campaign implemented a 3-hour bundle including blood cultures, lactate, intravenous fluids, and antibiotics to improve mortality in sepsis. Though difficult to achieve, bundle compliance is associated with decreased hospital mortality. We predict that the implementation of an Emergency Medical Services (EMS) sepsis screening tool will improve 3-hour bundle compliance.ObjectivesTo determine if pre-hospital sepsis screening improves 3-hour bundle compliance.MethodsProspective implementation of an EMS sepsis screening tool (June 2016–November 2016) was compared to a historical control (August 2015–March 2016). The protocol was facilitated via communication between nurses and EMS personnel. The primary outcome was 3-hour bundle compliance. Secondary outcomes included time to individual bundle components.ResultsOf 135 patients screened, 20 were positive and included in the study, and subsequently compared to 43 control patients. Baseline demographics were similar, except median Sequential Organ Failure Assessment (SOFA) score was higher for the pre-EMS tool group (5 [interquartile range (IQR) 2–8] vs. 2 [IQR 1–4], p < 0.01). Three-hour bundle compliance was significantly higher in the EMS tool group (80% vs. 44.2%, p < 0.01). The pre-EMS tool group had lower median time to lactate (15 [IQR 0–35] vs. 46 min [IQR 34–57], p < 0.001), 30 mL/kg IV fluids (6.5 [IQR 0–38] vs. 46 min [IQR 27.5–72], p < 0.001), and, although not significant, antibiotics (63.5 [IQR 44–92] vs. 72 min [IQR 59.5–112], p = 0.26).ConclusionImplementation of an EMS sepsis screening tool resulted in improved 3-hour bundle compliance compared to retrospective control.     

Hyperglycemia at presentation is associated with in hospital mortality in non-diabetic patient with organophosphate poisoning

Aims: This study evaluated whether the initial venous glucose level at presentation is associated with fatality in organophosphate (OP)-poisoned patients without diabetes mellitus (DM) and whether the association between glucose and outcome differs depending on the chemical formulation of the OP ingested. Methods: This retrospective observational case series consisted of 184 patients without DM who had a history of OP poisoning. Initial glucose level at presentation, outcome and general clinical data were recorded. The patients were categorized into the following groups according to their glucose level at presentation: group 1 (<140?mg/dl, n?=?63), group 2 (140–200?mg/dl, n?=?58), group 3 (200–300?mg/dl, n?=?41), and group 4 (≥300?mg/dl, n?=?22). The most commonly ingested OPs were dichlorvos (n?=?33), fenitrothion (n?=?25), and ethyl p-nitrophenol thio-benzene phosphonate (EPN) (n?=?24). The primary outcome was case fatality. Results: Group 4 had a higher case fatality than groups 1 (p?=?0.003) and 2 (p?=?0.015), and group 3 had a higher case fatality than group 1 (p?=?0.040). Multivariate analysis revealed that age [odds ratio (OR) 1.065, 95% confidence interval (CI) 1.020–1.112, p?=?0.001], being in group 3 (OR 6.997, 95% CI 1.063–46.066, p?=?0.043) and being in group 4 (OR 9.101, 95% CI 1.380–60.044, p?=?0.022) were associated with case fatality. When using the glucose level at presentation?>?233?mg/dl, the dichlorvos group had a higher sensitivity (66.7% vs. 50.0%), specificity (90.0% vs. 86.4%), and positive (40.0% vs. 25.0%) and negative (96.4% vs. 95.0%) predictive values for predicting case fatality than the EPN group. No patient died of fenitrothion poisoning (mean glucose level at presentation?=?169.4?±?39.6?mg/dl). Conclusion: The case fatality risk independently increases as the initial venous glucose level at presentation increases in OP-poisoned patients without DM. However, because the association between the venous glucose level at presentation and case fatality varies according to the type of OP ingested, the chemical identity of the OP should be considered.     

Incidence and patterns of cardiomyopathy in carbon monoxide-poisoned patients with myocardial injury

Objectives: Sustained myocardial injury is a significant predictor of mortality in carbon monoxide (CO) poisoning. There are few reports in the literature regarding the presence of CO-induced cardiomyopathy from early stages in the emergency department (ED). We prospectively investigated the early incidence of CO-induced cardiomyopathy and its patterns in patients with cardiomyopathy. Materials and methods: During a 10-month period, transthoracic echocardiography (TTE) was performed in 43 consecutive patients with CO poisoning and myocardial injury, which was defined as elevated high-sensitive troponin I within 24?h after ED arrival. Measurements of left ventricular ejection fraction and wall motion abnormalities were performed to evaluate cardiac function. If a patient had CO-induced cardiomyopathy, we measured cardiac function at the time of patient admission, day 1, day 2, and once within seven days of hospitalization. Results: The incidence of cardiomyopathy was as high as 74.4% (32 of 43 patients) in CO-poisoned patients with myocardial injury based on initial ED results. Echocardiographic patterns included non-cardiomyopathy (25.6%), global dysfunction (51.2%), and Takotsubo-like cardiomyopathy (23.2%). Patients in the global dysfunction group had significantly more normalized cardiac dysfunction within 72?h than did those in the Takotsubo-like cardiomyopathy group (81.8% vs. 22.2%, p?=?0.001). Discussion and conclusion: Patients with CO poisoning and myocardial injury experienced cardiomyopathy, including reversible global dysfunction and a Takotsubo-like pattern. Investigation of cardiomyopathy needs to be considered in patients with CO poisoning and myocardial injury.     

Impact of respiration gating on image integration guided atrial fibrillation ablation

Background

Radiofrequency (RF) catheter ablation guided by electroanatomic mapping systems is an effective therapy for atrial fibrillation. However, it may be affected by respiration movements. The aim of this study was to determine the impact of respiratory gating on procedural parameters in patients undergoing catheter ablation of atrial fibrillation (AF).

Methods and results

One-hundred forty consecutive patients undergoing pulmonary vein isolation were admitted to study. Respiratory gating module (AccuResp algorithm, Carto3, Biosense Webster) was enabled in 70 patients and disabled in 70 patients during procedures. Successful pulmonary vein isolation and sinus rhythm were obtained in all patients. A significant reduction in total procedure times [median 77, interquartile range (IQR 66–95) min vs median 82 (IQR 72–104) min, p < 0.05] and fluoroscopy times [median 14 (IQR 9–17) min vs median 16 (IQR 12–22) min, p < 0.05] were observed in the respiratory gated group. Although ablation times (duration between the first and last ablation) were significantly shorter in respiratory gated group [median 37 (IQR 32–53) min vs median 48 (IQR 39–65) min, p < 0.05], total RF application durations were not different between two groups [median 1,554 (IQR 1,213–2,196) s vs median 1,802 (IQR 1,344–2,448) s, p = 0.11]. Difference in electroanatomical map reconstruction times was not significant [median 14 (IQR 12–16) min in gated group vs median 13 (IQR 10–18) min in nongated group, p = 0.19].

Conclusion

Respiratory gating significantly improves fluoroscopy and ablation times during electroanatomic mapping guided AF ablation. Respiratory gated maps may provide uninterrupted continuous ablation applications. Furthermore, using automatic respiratory gating module does not prolong mapping times.     

Comparison of lower-dose versus higher-dose intravenous naloxone on time to recurrence of opioid toxicity in the emergency department

Introduction: The initial dose of naloxone administered to patients who present to the emergency department (ED) with opioid overdose is highly variable. The objective of this study was to determine if the initial dose of intravenous (IV) naloxone given to these patients was associated with the time to recurrence of opioid toxicity.

Methods: This was a multicenter retrospective cohort study, conducted at two academic EDs in the United States. Consecutive adults who had a positive response to naloxone for opioid overdose in the ED were included. Patients were categorized into two groups based on initial IV naloxone dose administered: 0.4?mg (lower-dose) or 1–2?mg (higher-dose). The main outcome measure was the time to recurrence of opioid toxicity requiring a second dose of naloxone. Secondary outcomes included the need for naloxone continuous infusion and adverse events.

Results: The study included 84 patients with 42 patients receiving lower-dose and 42 patients receiving higher-dose naloxone. Median time to re-dose of naloxone was similar between the lower-dose (72 [IQR 46–139] minutes) and higher-dose (70 [IQR 44–126] minutes) groups (p=.810). There were 12 patients (29%) in the lower-dose group and 17 patients (41%) in the higher-dose group who subsequently required continuous infusions (p=.359). The proportion of patients with adverse events was similar between lower-dose and higher-dose groups (31% versus 41%, p=.495). There was no difference in the incidence of specific withdrawal related adverse effects.

Conclusions: The initial dose of naloxone given to patients in the ED does not influence the time to recurrence of opioid toxicity.