Treatment of illicit opioid and γ-hydroxybutyrate overdose by Helsinki emergency medical services

Aims: To examine the characteristics, incidence, treatment and outcome of presumed opioid, γ-hydroxybutyrate (GHB) and γ-butyrolactone (GBL) overdoses involving users of illicit drugs in Helsinki. GHB/GBL were included in this study, despite not being opioids, due to the relative ease with which they can cause potentially fatal respiratory depression. The incidence and time interval of recurrent opioid toxicity after prehospital administration of naloxone, an opioid antagonist, was studied in presumed heroin overdose patients. Naloxone has been reported to have many adverse effects and the effects of naloxone administered during an opioid overdose on the cardiovascular system and catecholamine levels in piglets were studied. Materials and methods: Patients included in these published retrospective studies were from the following time periods: Study I: 1995-2002, II: 1997-2000, III: 1995-2000, V: 2006-2007. Presumed opioid overdose patients were examined in studies I, II and III. GHB/GBL overdoses among injecting drug users was examined in study V. Recurrent opioid toxicity after prehospital naloxone administration in heroin overdose patients was examined in study III. The effects of naloxone (80 μg/kg i.v.) on the cardiovascular system and catecholamine levels administered during morphine overdose (8mg/kg i.v.) and under propofol anesthesia with spontaneous breathing were studied in eight piglets (IV). In this thesis, previously unpublished data on the incidence of opioid overdose between 2001-2007 and comparison of the characteristics of buprenorphine and heroin overdose patients encountered in 1995-2005 are also included. Results: Helsinki Emergency Medical Service (EMS) ambulances were dispatched annually to 34,153- 45,118 calls from 1995 to 2007. Of them, 7-8% were coded as intoxications or overdoses. During this time, 436 patients were treated by the EMS for presumed opioid overdose. The peak incidence of opioid overdoses was in the year 2000 (113 cases), after which they declined to 6-26 cases annually. The annual incidence of buprenorphine related overdoses increased from 4 (4% of opioid overdoses) in the year 2000 to 8 (30% of opioid overdoses) in 2007. The annual number of GHB related overdose patients treated by Helsinki EMS increased from 21 to 73 between 2004-2007. There appeared to be a peak in the incidence of both GHB/GBL and opioid related overdoses on Saturdays. Characteristics of opioid overdose patients The median age of opioid overdose patients was 28 years (22;33, 25- and 75-percentiles), and 84% were male. Buprenorphine overdose patients had more polydrug, such as alcohol and/or benzodiazepines, use in comparison with heroin overdose patients, 70% versus 33%, respectively. Severe respiratory depression was reported less often with buprenorphine overdoses compared to heroin overdoses, in 67.0% versus 85.4%, respectively. Outcome of heroin overdose patients with cardiac arrest Ninety four patients suffered cardiac arrest due to acute drug poisoning/overdose and were thus considered for resuscitation. Resuscitation was attempted in 72 cases. Cardiac arrest was caused by heroin overdose for 19 patients of which three (16%) were discharged alive. Other agents also induced cardiac arrest in 53 patients, of which six (11%) were discharged alive. The arrest was either EMS witnessed or occurring after the emergency call for all survivors of heroin induced cardiac arrest. Characteristics of GHB/GBL overdose patients The records of 100 GHB/GBL related overdose patients from 2006-2007 were retrieved. The median age of GHB/GBL overdose patients encountered on weekend nights was 24 years (22;27, 25- and 75-percentiles) and 49% were male. Polydrug use was reported in 62-80% of the cases. Thirty nine patients were encountered on Friday-Saturday or Saturday-Sunday night between 11 pm-6 am. The remaining sixty one patients were outside this time frame. There was a statistically significant difference between these two groups in history of chronic injecting drug use (33% vs. 59%, respectively, p=0.012). Recurrent heroin toxicity after prehospital naloxone administration Study III included 145 presumed heroin overdose patients. After prehospital care, 84 patients refused further care and were not transported to an Emergency Department (ED). Seventy one (85%) of them were administered naloxone by the EMS. During a 12-h follow up period, none of these patients developed severe recurrent opioid toxicity. The remaining 61 patients were transported to an ED. Prior to transportation, 52 (85%) patients were administered naloxone by the EMS. Fifteen of them were administered naloxone also in the ED and recurrent opioid toxicity was evident either on arrival at the ED or shortly thereafter. Prehospital naloxone was administered either intravenously, intramuscularly (i.m.) or subcutaneously (s.c.). There was a tendency for more frequent recurrent heroin toxicity among the patients with only intravenous administration of prehospital naloxone (13/36) compared with the patients with intramuscular or subcutaneous prehospital naloxone (2/16), p=0.106. The effects of naloxone on the cardiovascular system and catecholamine levels in piglets The administration of morphine to piglets resulted in an obvious respiratory depression, which was reversed by naloxone. Two severely hypoxemic piglets developed cardiac arrest after naloxone administration. In the other six animals, the administration of naloxone did not provoke arrhythmias, cardiac ischemia or visible evidence of pulmonary edema. There was a statistically significant (p=0.012) increase in norepinephrine levels after morphine administration and before naloxone administration: from 1.9 (1.3-2.3) ng/ml at baseline, to 31.7 (8.3-83.0) ng/ml (median, 25 and 75 percentiles parentheses) after morphine administration. After the administration of naloxone, the catecholamine levels continued to increase in only one of the animals. Conclusions: The incidence of buprenorphine related overdoses increased during the study period, but was still lower in comparison to those involving heroin. Injecting drug users have also started to use GHB/GBL. While recreational drug users use GHB/GBL during weekend nights, a GHB/GBL overdose patient encounter during weekdays has a more probable history of injecting drug use. Patients with cardiac arrest after heroin overdose have a poor prognosis. It appears to be safe to leave heroin overdose patients on scene after prehospital treatment with naloxone. Although no statistically significant difference was observed, it seems prudent to administer part of the total naloxone dose s.c. or i.m. to reduce the risk of recurrent respiratory depression. If transported to an ED, an observation period of one to two hours after the last naloxone dose seems adequate. The treating physician must be vigilant, however, due to the high prevalence of polydrug use and high morbidity after non fatal heroin overdose. Furthermore, care should be taken regarding possible chronic disorders and drug rehabilitation should be addressed. In the experimental animal study, two animals developed cardiac arrest after receiving naloxone while in hypoxemia and bradycardia. Further studies are required to assess the effect of naloxone during opioid-induced hypercapnia and hypoxemia in animals addicted to opioids.

Bystander resuscitation attempts at heroin overdose: does it improve outcomes?

Study objective: To document the characteristics and effectiveness of cardiopulmonary resuscitation (CPR) at non-fatal heroin overdose events in Melbourne, Australia. Methods: A retrospective analysis of a computerised database of ambulance attendance records at non-fatal heroin overdose cases for the period 1/12/1998 to 31/7/2000 was undertaken.

Main outcome measures: The main outcome measure was the rate of patient hospitalisation. The rate of CPR administration at heroin overdose cases was also examined, along with characteristics of the attendance, such as the age and sex of the overdose case, the relationship of person providing CPR to the overdose case as well as the location, time and date of the event.

Results: CPR was administered prior to ambulance arrival in 579 heroin overdose cases (9.4% of total heroin overdose cases attended) between 1/12/98 and 31/7/2000. A greater proportion of female overdose cases were administered CPR than males and CPR administrations were evenly distributed across attendances occurring in private and public locations. Bystander administration of CPR prior to ambulance attendance resulted in a significantly lower rate of heroin user hospitalisation (14.5%) compared to cases where bystander CPR was not administered (18.8%).

Conclusions: While CPR administration prior to ambulance attendance at heroin overdose events is relatively uncommon (especially compared to out-of-hospital cardiac arrest), such administration was associated with a statistically significant improvement in clinical outcomes in cases of non-fatal heroin overdose. These findings suggest that the provision of CPR training to people likely to come into contact with heroin overdose events may be an effective strategy at minimising consequent overdose-related harm.

Patterns and Characteristics of Ambulance Attendance at Heroin Overdose at a Local-Area Level in Melbourne, Australia: Implications for Service Provision

The monitoring of heroin use and related harms is undertaken in Australia with a view to inform policy responses. Some surveillance data on heroin-related harms is well suited to inform the planning and delivery of heroin-related services, such as needle and syringe provision. This article examines local-area variation in the characteristics of nonfatal heroin overdoses attended by ambulances in Melbourne over the period June 1998 to October 2000 to inform the delivery of services to the heroin-using population in Melbourne.

Intentional overdose among heroin overdose survivors

Previous studies have reported varying rates of intentional overdose among heroin overdose survivors. This article reports on the prevalence of intentional heroin overdose among a sample of overdose survivors in Melbourne, Australia. This is part of a larger study examining the risk factors associated with nonfatal overdose. The study involved interviews, with 256 heroin overdose survivors successfully resuscitated by Melbourne Ambulance Service paramedics. A substantial minority (17%) of the sample indicated that they had ever had an intentional overdose, and 67% had one within the last 6 months (11% of the total sample). Of those who had ever intentionally overdosed, 21% did so at the overdose for which they were recruited into the study (4% of total sample). Self-reported reasons for intentional heroin overdose fell into two categories: precipitating events and emotional states prior to use. Intentional overdose appears to comprise a relatively low proportion of overall heroin overdoses. However, given the complexity of suicidal thought and behavior, it is possible that some heroin overdose survivors who report their overdose to be unintentional were in fact experiencing some degree of suicidal thinking at the time of the overdose. Future research could address the potentially ambiguous nature of some intentional heroin overdoses.

Drug overdose: widening the parameters of research and prevention

[A focus on risk environments] helps to overcome the limits of individualism characterising most [drug] prevention interventions as well as to appreciate how drug-related harm intersects with health and vulnerability more generally.

Media reports of heroin overdose spates: public health messages, moral panics or risk advertisements?

This article reports on an investigation of the public health utility of media messages concerning spates (temporal clusters) of heroin-related overdose (HOD) from the perspective of some injecting drug users (IDUs). In-depth qualitative interviews were carried out with a convenience sample of 60 IDUs, in the setting of two Needle and Syringe Programs in an Australian regional city (Geelong) between April and May 2000. Very few interviewees reported that they had personally experienced a spate of overdoses. None of the interviewees reported communicating the existence of a killer batch to other IDUs. No interviewees reported having changed either their injecting practices or the amount of heroin they used following such a media alert. Indeed, a substantial minority of the interviewees reported seeking out these stronger batches and participant narratives illustrate that, for a substantial group of interviewees, the media reporting of a hypothetical 'killer batch' of heroin may have implications for their drug-seeking and health-related behaviour. It was found that the accuracy of information available to IDUs is mixed and that the flow of information within this social network was slow. Findings demonstrate that media reporting of killer batches of heroin has little value as a public health strategy and provide an example of how some activities that are proposed as public health measures may in fact have the opposite effect.

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.

Análise dos processos de decomposição e sucessão ecológica em carcaças de suínos (Sus scrofa L.) mortos por disparo de arma de fogo e overdose de cocaína e protocolo de procedimento diante de corpo de delito

Pós-graduação em Biologia Geral e Aplicada - IBB

Gastric pharmacobezoars in quetiapine extended-release overdose: a case series

OBJECTIVE Although extended-release (XR) formulations are recognized to bear some risk of pharmacobezoar formation in overdose, there are no previously documented reports of this phenomenon with quetiapine. We describe nine cases of pharmacobezoar formation in acute quetiapine XR overdose. METHODS Observational case series of all patients who underwent gastroscopy after quetiapine XR overdose, which were reported by physicians to the Swiss Toxicological Information Centre between January 2010 and December 2012, with detailed analysis of cases with documented pharmacobezoar. RESULTS Gastric pharmacobezoars were detected in 9 out of 19 gastroscopic evaluations performed during the study period. All these patients ingested a large dose of quetiapine XR (10-61 tablets; 6-24.4 g quetiapine). All patients but one also coingested at least one other substance, and in three cases another XR drug formulation. Gastroscopic pharmacobezoar removal was achieved without complications in all patients, but was difficult due to the particular "gelatinous-sticky-pasty" consistency of the concretion. The subsequent clinical course was favorable. CONCLUSIONS The possibility of pharmacobezoar formation following a large quetiapine XR overdose should be considered, as this may influence acute patient management. Complete endoscopic pharmacobezoar removal may be a promising approach in selected cases, but further studies are needed to define its role.

Pharmacokinetics of meprobamate in overdose treated with continuous venovenous hemodiafiltration (CVVHDF)

We report a case of massive suicidal overdose of meprobamate leading to cardiovascular collapse, respiratory failure, and severe central nervous system depression. We observed first-order elimination kinetics despite significant overdose, and demonstrated effectiveness of continuous venovenous hemodiafiltration (CVVHDF) for extracorporeal removal of meprobamate in this patient. Total body clearance was calculated to be 87 mL/minute, with 64 mL/minute (74%) due to CVVHDF. CVVHDF was stopped after 36 hours, and the patient made an uneventful recovery.