Out-of-hospital Treatment of Opioid Overdoses in an Urban Setting

Objectives : To investigate clinical outcomes in a cohort of opioid overdose patients treated in an out-of-hospital urban setting noted for a high prevalence of IV opioid use. Methods : A retrospective review was performed of presumed opioid overdoses that were managed in 1993 by the emergency medical services (EMS) system in a single-tiered, urban advanced life support (ALS) EMS system. Specifically. all patients administered naloxone by the county paramedics were reviewed. Those patients with at least 3 of 5 objective criteria of an opioid overdose [respiratory rate <6/min, pinpoint pupils, evidence of IV drug use, Glasgow Coma Scale (GCS) score <12, or cyanosis] were included. A response to naloxone was defined as improvement to a GCS 14 and a respiratory rate 10/min within 5 minutes of naloxone administration. ED dispositions of opioid-overdose patients brought to the county hospital were reviewed. All medical examiner's cases deemed to be opioid-overdose-related deaths by postmortem toxicologic levels also were reviewed. Results : There were 726 patients identified with presumed opioid overdoses. Most patients (609/726, 85.4%) had an initial pulse and blood pressure (BP). Most (94%) of this group responded to naloxone and all were transported. Of the remainder, 101 (14%) had obvious signs of death and 16 (2.2%) were in cardiopulmonary arrest without obvious signs of death. Of the patients in full arrest, 2 had return of spontaneous circulation but neither survived. Of the 609 patients who had initial BPs, 487 (80%) received naloxone IM (plus bag-valve-mask ventilation) and 122 (20%) received the drug IV. Responses to naloxone were similar; 94% IM vs 90% IV. Of 443 patients transported to the county hospital, 12 (2.7%) were admitted. The admitted patients had noncardiogenic pulmonary edema (n = 4). pneumonia (n = 2), other infections (n = 2), persistent respiratory depression (n = 2). and persistent alteration in mental status (n = 2). The patients with pulmonary edema were clinically obvious upon ED arrival. Hypotension was never noted and bradycardia was seen in only 2% of our presumed-opioid:overdose population. Conclusions : The majority of the opioid-overdose patients who had initial BPs responded readily to naloxone, with few patients requiring admission. Noncardiogenic pulmonary edema was uncommon and when present, hypoxia was evident upon arrival to the ED. Naloxone administered IM in conjunction with bag-valve-mask ventilation was effective in this patient population. The opioid-overdose patients in cardiopulmonary arrest did not survive.     

Naloxone Use in a Tiered-Response Emergency Medical Services System

Objective. To examine the delivery andeffect of naloxone for opioid overdose in a tiered-response emergency medical services (EMS) system andto ascertain how much time could be saved if the first arriving emergency medical technicians (EMTs) could have administered intranasal naloxone. Methods. This was case series of all EMS-treated overdose patients who received naloxone by paramedics in a two-tiered EMS system during 2004. The system dispatches basic life support–trained fire fighter–EMTs and/or advanced life support–trained paramedics depending on the severity of cases. Main outcomes were geographic distribution of naloxone-treated overdose, severity of cases, response to naloxone, andtime interval between arrival of EMTs andarrival of paramedics at the scene. Results. There were 164 patients who received naloxone for suspected overdose. There were 75 patients (46%) initially unresponsive to painful stimulus. Respiratory rate was <10 breaths/min in 79 (48%). Death occurred in 36 (22%) at the scene or during transport. A full or partial response to naloxone occurred in 119 (73%). Recognized adverse reactions were limited to agitation/combativeness in 25 (15%) andemesis in six (4%). Average EMT arrival time was 5.9 minutes. Average paramedic arrival time was 11.6 minutes in most cases and16.1 minutes in 46 cases (28%) in which paramedics were requested by EMTs at the scene. Conclusions. There is potential for significantly earlier delivery of naloxone to patients in opioid overdose if EMTs could deliver intranasal naloxone. A pilot study training andauthorizing EMTs to administer intranasal naloxone in suspected opioid overdose is warranted.     

Early Discharge of Patients with Presumed Opioid Overdose: Development of a Clinical Prediction Rule

OBJECTIVE: To develop a clinical prediction rule to identify patients who can be safely discharged one hour after the administration of naloxone for presumed opioid overdose. METHODS: Patients who received naloxone for known or presumed opioid overdose were formally evaluated one hour later for multiple potential predictor variables. Patients were classified into two groups: those with adverse events within 24 hours and those without. Using classification and regression tree methodology, a decision rule was developed to predict safe discharge. RESULTS: Clinical findings from 573 patients allowed us to develop a clinical prediction rule with a sensitivity of 99% (95% CI = 96% to 100%) and a specificity of 40% (95% CI = 36% to 45%). Patients with presumed opioid overdose can be safely discharged one hour after naloxone administration if they: 1) can mobilize as usual; 2) have oxygen saturation on room air of >92%; 3) have a respiratory rate >10 breaths/min and <20 breaths/min; 4) have a temperature of >35.0 degrees C and <37.5 degrees C; 5) have a heart rate >50 beats/min and <100 beats/min; and 6) have a Glasgow Coma Scale score of 15. CONCLUSIONS: This prediction rule for safe early discharge of patients with presumed opioid overdose performs well in this derivation set but requires validation followed by confirmation of safe implementation.     

Terbutaline vs Albuterol for Out-of-hospital Respiratory Distress: Randomized, Double-blind Trial

Objective: To determine the efficacy and safety of single doses of subcutaneous terbutaline (terb) or nebulized albuterol (alb) during out-of-hospital treatment for respiratory distress from asthma or chronic obstructive pulmonary disease.
Methods: Patients aged >18 years who had respiratory distress were enrolled in a double-placebo, double-blind, randomized trial. Paramedics measured respiratory severity using an empiric score [respiratory rate, wheezing, speech, and peak expiratory flow rate (PEFR)], and the patients rated their own respiratory distress using a visual analog scale (VAS). The patients received 0₂ plus alb (2.5 mg) and saline injection ( n = 40) or terb (0.25 mg) and saline aerosol ( n = 43).
Results: The groups were similar with respect to age, gender, initial empiric scores (median score 9 for both groups), PEFRs (89 ± 84 L/min, mean ± SD, for alb vs 97 ± 84 L/min for terb), and respiratory distress VAS scores. Both groups showed significant improvement in their respiratory distress VAS scores by the time of ED arrival. The alb group had a greater improvement in respiratory distress VAS score than did the terb group (p < 0.05). Empiric scores, PEFR scores, and hospital admission frequencies were not significantly different. No complication was observed.
Conclusion: The out-of-hospital administration of either aerosolized alb or subcutaneous terb reduced respiratory severity. Albuterol provided greater subjective improvement in respiratory distress.     

Intranasal Naloxone Is a Viable Alternative to Intravenous Naloxone for Prehospital Narcotic Overdose

Objective. To compare the prehospital time intervals from patient contact and medication administration to clinical response for intranasal (IN) versus intravenous (IV) naloxone in patients with suspected narcotic overdose. Methods. This was a retrospective review of emergency medical services (EMS) and hospital records, before and after implementation of a protocol for administration of intranasal naloxone by the Central California EMS Agency. We included patients with suspected narcotic overdose treated in the prehospital setting over 17 months, between March 2003 and July 2004. Paramedics documented dose, route of administration, and positive response times using an electronic record. Clinical response was defined as an increase in respiratory rate (breaths/min) or Glasgow Coma Scale score of at least 6. Main outcome variables included time from medication to clinical response and time from patient contact to clinical response. Secondary variables included numbers of doses administered and rescue doses given by an alternate route. Between-group comparisons were accomplished using t-tests and chi-square tests as appropriate. Results. One hundred fifty-four patients met the inclusion criteria, including 104 treated with IV and 50 treated with IN naloxone. Clinical response was noted in 33 (66%) and 58 (56%) of the IN and IV groups, respectively (p = 0.3). The mean time between naloxone administration and clinical response was longer for the IN group (12.9 vs. 8.1 min, p = 0.02). However, the mean times from patient contact to clinical response were not significantly different between the IN and IV groups (20.3 vs. 20.7 min, p = 0.9). More patients in the IN group received two doses of naloxone (34% vs. 18%, p = 0.05), and three patients in the IN group received a subsequent dose of IV or IM naloxone. Conclusions. The time from dose administration to clinical response for naloxone was longer for the IN route, but the overall time from patient contact to response was the same for the IV and IN routes. Given the difficulty and potential hazards in obtaining IV access in many patients with narcotic overdose, IN naloxone appears to be a useful and potentially safer alternative.     

Suspected opioid-related emergency medical services encounters in a rural state, 1997-2002

Introduction

News organizations and governmental agencies have reported substantial increases in the number of opioid-related overdose cases in recent years.

Objective

To describe the utilization of emergency medical services (EMS) for suspected opioid-related overdose cases in a rural state during the period 1997 through 2002.

Methods

Statewide EMS records were reviewed for 1997 through 2002. Data reviewed included prehospital diagnosis and medications given to all patients by prehospital providers. For cases with a prehospital diagnosis of poisoning or overdose, data reviewed included medications given to patients by prehospital providers, pupil size, and respiratory rate. All records were reviewed in a defined sequence.

Results

The study period encompassed 1,175,781 patient encounters. Poisoning or overdose patients accounted for 19,808 (1.7%) encounters. Naloxone was administered by the EMS provider to 2,668 (0.2%) patients. For all poisoning or overdose patients, 1,308 (6.6%) had miotic pupils, 450 (2.2%) had a respiratory rate of <12 breaths/min, and 1,569 (7.9%) received naloxone. During the investigation period, total EMS patient encounters increased 25%, while patients with a complaint of poisoning or overdose increased 47%. The incidences of EMS overdose patients with miotic pupils, respiratory rate <10 breaths/min, and naloxone administration increased 167%, 295%, and 154%, respectively.

Conclusion

In this rural state, prehospital patients with findings suspicious for opioid overdose disproportionately outpaced the growth of all EMS encounters as well as general overdose encounters during the defined investigation period.     

Assessment for Deaths in Out-of-hospital Heroin Overdose Patients Treated with Naloxone Who Refuse Transport

Naloxone frequently is used to treat suspected heroin and opioid overdoses in the out-of-hospital setting. The authors' emergency medical services system has operated a policy of allowing these patients, when successfully treated, to sign out against medical advice (AMA) in the field. OBJECTIVES: To evaluate the safety of this AMA policy. METHODS: This is a retrospective review of out-of-hospital and medical examiner (ME) databases over a five-year period. The authors reviewed all ME cases in which opioid overdoses were listed as contributing to the cause of death. These cases were cross-compared with all patients who received naloxone by field paramedics and then refused transport. The charts were reviewed by dates, times, age, sex, location, and ethnicity when available. RESULTS: There were 998 out-of-hospital patients who received naloxone and refused further treatment and 601 ME cases of opioid overdose deaths. When compared by age, time, date, sex, location, and ethnicity, there were no cases in which a patient was treated by paramedics with naloxone within 12 hours of being found dead of an opioid overdose. CONCLUSIONS: Giving naloxone to patients with heroin overdoses in the field and then allowing them to sign out AMA resulted in no identifiable deaths within this study population.     

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.     

Adverse events after naloxone treatment of episodes of suspected acute opioid overdose.

OBJECTIVE: An increasing and serious heroin overdose problem in Oslo has mandated the increasing out-of-hospital use of naloxone administered by paramedics. The aim of this study was to determine the frequencies and characteristics of adverse events related to this out-of-hospital administration by paramedics. METHODS: A one-year prospective observational study from February 1998 to January 1999 was performed in patients suspected to be acutely overdosed by an opioid. A total of 1192 episodes treated with naloxone administered by the Emergency Medical Service system in Oslo, were included. The main outcome variable was adverse events observed immediately after the administration of naloxone. RESULTS: The mean age of patients included was 32.6 years, and 77% were men. Adverse events suspected to be related to naloxone treatment were reported in 45% of episodes. The most common adverse events were related to opioid withdrawal (33%) such as gastrointestinal disorders, aggressiveness, tachycardia, shivering, sweating and tremor. Cases of confusion/restlessness (32%) might be related either to opioid withdrawal or to the effect of the heroin in combination with other drugs. Headache and seizures (25%) were probably related to hypoxia. Most events were non-serious. In three episodes (0.3%) the patients were hospitalized because of adverse events. CONCLUSION: Although adverse events were common among patients treated for opioid overdose in an out-of-hospital setting, serious complications were rare. Out-of-hospital naloxone treatment by paramedics seems to save several lives a year without a high risk of serious complications.     

Intranasal naloxone delivery is an alternative to intravenous naloxone for opioid overdoses

Introduction

This study proposes that intranasal (IN) naloxone administration is preferable to intravenous (IV) naloxone by emergency medical services for opioid overdoses. Our study attempts to establish that IN naloxone is as effective as IV naloxone but without the risk of needle exposure. We also attempt to validate the use of the Glasgow Coma Scale (GCS) in opioid intoxication.

Methods

A retrospective chart review of prehospital advanced life support patients was performed on confirmed opioid overdose patients. Initial and final unassisted respiratory rates (RR) and GCS, recorded by paramedics, were used as indicators of naloxone effectiveness. The median changes in RR and GCS were determined.

Results

Three hundred forty-four patients who received naloxone by paramedics from January 1, 2005, until December 31, 2007, were evaluated. Of confirmed opioid overdoses, change in RR was 6 for the IV group and 4 for the IN group (P = .08). Change in GCS was 4 for the IV group and 3 for the IN group (P = .19). Correlations between RR and GCS for initial, final, and change were significant at the 0.01 level (ρ = 0.577, 0.462, 0.568, respectively).

Conclusion

Intranasal naloxone is statistically as effective as IV naloxone at reversing the effects of opioid overdose. The IV and IN groups had similar average increases in RR and GCS. Based on our results, IN naloxone is a viable alternative to IV naloxone while posing less risk of needle stick injury. Additionally, we demonstrated that GCS is correlated with RR in opioid intoxication.     

Pentazocine (Talwin) intoxication: report of 57 cases

Overdose of pentazocine (Talwin), an agonist/antagonist opioid analgesic, is relatively uncommon. Fifty-seven cases occurring over ten years are reported. Twenty-three patients (40%) had ingested only pentazocine and did not have the classic opioid toxidrome of CNS and respiratory depression with miosis. Most patients were awake, and no patient had a respiratory rate below 12/minute. Other findings included: grand mal seizures, hypertension, hypotonia, dysphoria, hallucinations, delusions, and agitation. Eleven of 23 patients received IV naloxone (0.4-2.4 mg), but only two showed improvement. Thirty-four patients (60%) had coingested pentazocine with one to five additional substances. Patients who had ingested pentazocine with alcohol, a sedative/hypnotic drug, or an antihistamine, showed increased toxicity, including apnea, deep coma, and recurrent seizures. One patient developed opioid pulmonary edema. One patient died. Three of five patients with coma and inadequate respirations responded to IV naloxone in doses of 0.4 to 1.2 mg.     

Self-reported Pain Scores in the Emergency Department: Lack of Association with Vital Signs

Background: Some practitioners and investigators have presumed relationships between pain scores and heart rate, blood pressure, or respiratory rate. Previous literature has not adequately addressed the association of pain and vital signs.
Objectives: To identify any association between self-reported pain and heart rate, blood pressure, or respiratory rate.
Methods: In this retrospective, observational study, emergency department patients older than 17 years of age presenting between May 2004 and April 2005 with verifiable painful diagnoses (including nephrolithiasis, myocardial infarction, small bowel obstruction, fracture, burn, crush injury, stab wound, amputation, corneal abrasion, and dislocation) were identified. Data were extracted from the hospital's database, including patients' age, gender, emergency department diagnosis, self-reported pain score, heart rate, blood pressure, and respiratory rate.
Results: Among 1,063 subjects, the most common diagnoses were nephrolithiasis (25%; n = 267) and fracture (23%; n = 249). The mean (± SD) triage pain score was 7 (± 3). The mean (± SD) heart rate was 85 (± 16) beats/min, mean (± SD) systolic blood pressure was 141 (± 23) mm Hg, and mean (± SD) respiratory rate was 19 (± 3) breaths/min. There were no clinically significant differences in mean vital signs across the individual pain scores, as demonstrated by overlapping confidence intervals across pain scores.
Conclusions: No clinically significant associations were identified between self-reported triage pain scores and heart rate, blood pressure, or respiratory rate.     

连续气道正压通气和高流量湿化氧疗方式下患者行纤维支气管镜诊疗的临床观察

目的探讨连续气道正压通气（CPAP）和高流量湿化氧疗（HFHCO）方式下患者行纤维支气管镜操作的临床效果。 方法选择2018年12月至2019年7月使用纤维支气管镜诊疗的26例留置人工气道患者,根据患者行纤维支气管镜的操作次数,将其分为CPAP组（32例次）和HFHCO组（32例次）。比较两组患者在纤维支气管镜诊疗操作前及诊疗操作过程中心率、呼吸频率、平均动脉压、外周动脉血氧饱和度（SaO₂）以及操作前后患者血液pH值、动脉血氧分压（PaO₂）、动脉血二氧化碳分压（PaCO₂）、脉搏血氧饱和度（SpO₂）。记录两组患者在行纤维支气管镜诊疗中的不良反应发生情况。 结果操作中,HFHCO组患者心率[（121 ± 3）次/ min vs.（130 ±3）次/ min]、呼吸频率[（21.3 ± 2.7）次/ min vs.（26.1 ± 2.3）次/ min]及平均动脉压[（99 ± 7）mmHg vs.（109 ± 8）mmHg]均较CPAP组患者显著降低（t = 5.232、5.164、6.424,P均< 0.001）。操作后,CPAP组和HFHCO组患者pH值[（7.45 ± 0.05）vs.（7.45 ± 0.07）]、PaO₂ [（86.5 ± 7.3）mmHg vs.（88.3 ±6.7）mmHg]、PaCO₂ [（40.1 ± 7.5）mmHg vs.（39.4 ± 6.8）mmHg]及SpO₂ [（93.9 ± 2.4）% vs.（94.1 ± 2.0）%]水平比较,差异均无统计学意义（t = 0.222、0.468、0.420、0.348,P = 0.731、0.670、0.684、0.697）。与同组操作前比较,CPAP组和HFHCO组患者操作中心率[（86 ± 4）次/ min vs.（130 ± 3）次/ min,（87 ± 4）次/ min vs.（121 ± 3）次/ min,t = 9.826、9.612,P均< 0.001]、呼吸频率[（17.8 ± 2.5）次/ min vs.（26.1 ± 2.3）次/ min,（16.7 ± 2.9）次/ min vs.（21.3 ± 2.7）次/ min,t = 8.488、5.837,P均< 0.001]及平均动脉压[（78 ± 7）mmHg vs.（109 ± 8）mmHg,（77 ± 7）mmHg vs.（99 ± 7）mmHg,t = 9.104、8.224,P均< 0.001]及操作后PaO₂ [（67.8 ± 2.6）mmHg vs.（86.5 ± 7.3）mmHg,（68.9 ± 4.0）mmHg vs.（88.3 ± 6.7）mmHg,t = 7.126、6.395,P均< 0.001]水平均显著升高。两组患者在进行纤维支气管镜诊疗操作过程中均未发生严重出血、恶性心律失常、气胸等事件。 结论对于留置气管插管或气管切开留置套管的患者,在应用CPAP或HFHCO给氧方式下行纤维支气管镜操作时均可改善患者气道通气,提高患者PaO₂,但是HFHCO给氧方式下患者的舒适度更好,减轻了患者呼吸、血流动力学体征的明显波动。     

Dextromethorphan poisoning reversed by naloxone

Dextromethorphan, a common ingredient in cough syrups, has rarely been described to cause toxicity. The authors describe an unusual case of a known asthmatic presenting with somnolence, who appeared to be in end-stage respiratory failure. Her partial response to routine naloxone, 1 mg, was surprising. However, additional naloxone was required to completely normalize the patient's mental status. The authors suggest naloxone be administered in doses of 0.4 mg or more intravenously in suspected dextromethorphan overdose.     

Measuring a Crisis: Questioning the Use of Naloxone Administrations as a Marker for Opioid Overdoses in a Large U.S. EMS System

Objective: The United States is currently experiencing a public health crisis of opioid overdoses. To determine where resources may be most needed, many public health officials utilize naloxone administration by EMS as an easily-measured surrogate marker for opioid overdoses in a community. Our objective was to evaluate whether naloxone administration by EMS accurately represents EMS calls for opioid overdose. We hypothesize that naloxone administration underestimates opioid overdose. Methods: We conducted a chart review of suspected overdose patients and any patients administered naloxone in Wake County, North Carolina, from January 2013 to December 2015. Patient care report narratives and other relevant data were extracted from electronic patient care records and the resultant database was analyzed by two EMS physicians. Cases were divided into categories including “known opioid use,” “presumed opioid use,” “no known opioid,” “altered mental status,” “cardiac arrest with known opioid use,” “cardiac arrest with no known opioid use,” or “suspected alcohol intoxication,” and then further separated based on whether naloxone was administered. Patient categories were compared by patient demographics and incident year. Using the chart review classification as the gold standard, we calculated the sensitivity and positive predictive value (PPV) of naloxone administration for opioid overdose. Results: A total of 4,758 overdose cases from years 2013–15 were identified. During the same period, 1,351 patients were administered naloxone. Of the 1,431 patients with known or presumed opioid use, 57% (810 patients) received naloxone and 43% (621 patients) did not. The sensitivity of naloxone administration for the identification of patients with known or presumed opioid use was 57% (95% CI: 54%–59%) and the PPV was 60% (95% CI: 57%–63%). Conclusion: Among patients receiving care in this large urban EMS system in the United States, the overall sensitivity and positive predictive value for naloxone administration for identifying opioid overdoses was low. Better methods of identifying opioid overdose trends are needed to accurately characterize the burden of opioid overdose within and among communities.     

Wooden chest syndrome: Beware of opioid antagonists,not just agonists

BackgroundIn a constantly increasing world of opioid addiction, naloxone has become a topic of great discussion and use. With seemingly minimal side effects, naloxone has become one of the most wellknown and widely used reversal agents for opioid intoxication. While more common effects of using naloxone include agitation, abdominal cramps, piloerection, diarrhea, nausea, and yawning, lesser known side effects involve muscle spasms, flushing, hyperreflexia in neonates, and seizures. This case study demonstrates a side effect of rigidity secondary to IV naloxone that has not previously been documented.CaseA 56 year old man was brought in by EMS after being found unresponsive in a car with a bag of drugs beside him. He was given 0.5 mg naloxone IV by EMS and immediately brought to the hospital. On arrival, the pt was noted to have tight rigidity of his upper extremities, with severe flexion. This presentation was not noted before the delivery of naloxone by EMS.ConclusionsWhile this case highlights a patient with a rare side effect of naloxone, it reminds physicians that all medications come with a cost. Of course, ABCs remain the highest priority of resuscitation, however when administering a medication to reverse a drug overdose, it is important to keep in mind all possible consequences of said agent. Recognizing that complete muscle rigidity may remain a result of naloxone administration allows physicians to perhaps save patients from further medical workup.     

Use and efficacy of nebulized naloxone in patients with suspected opioid intoxication

ObjectiveTo describe the use and efficacy of nebulized naloxone in patients with suspected opioid intoxication.MethodsThis was an observational study conducted at an inner city emergency department. Patients were eligible if they had self-reported or suspected opioid intoxication and a spontaneous respiratory rate ≥ 6 breaths/minute. Nebulized naloxone (2 mg in 3 mL normal saline) was administered through a standard face mask at the discretion of the treating physician. Structured data collection included demographics, vital signs pre and post naloxone administration and adverse events. The primary outcome was level of consciousness, which was recorded pre and 15 minutes postnaloxone administration using the Glasgow Coma Scale (GCS) and the Richmond Agitation Sedation Scale (RASS).ResultsOf the 73 patients who presented with suspected opioid intoxication and were given naloxone over the study period, 26 were initially treated with nebulized naloxone. After nebulized naloxone administration, median GCS improved from 11 [interquartile range (IQR) 3.5] to 13 (IQR, 2.5), P = .001. Median RASS improved from ? 3.0 (IQR, ? 1.0) to ? 2.0 (IQR, ? 1.5), P < .0001. Need for supplemental oxygen decreased from 81% to 50%, P = .03. Vital signs did not differ pre/post therapy. There were few adverse effects from nebulized naloxone administration: 12% experienced moderate-severe agitation, 8% were diaphoretic and none vomited. Eleven required subsequent administrations of naloxone, nine of whom self-reported using either heroin, methadone or both. Of these, 5 underwent urine drug screening and all 5 tested positive for either opiates or methadone.ConclusionsNebulized naloxone was well-tolerated and led to a reduction in the need for supplemental oxygen as well as improved median GCS and RASS scores in patients with suspected opioid intoxication.     

Effects of Cardiac Resynchronization Therapy on Heart Rate Turbulence

Background: Cardiac resynchronization therapy (CRT) improves the clinical status of patients with heart failure (HF), though its effects on heart rate turbulence (HRT) are unknown.
Methods: We measured HRT indices in 58 recipients of CRT systems (mean age = 56 ± 9 years, 41 men) in New York Heart Association HF functional class III–IV, and with a left ventricular (LV) ejection fraction ≤35%. At 6 months of follow-up, 42 patients were responders and 13 nonresponders to CRT, and three patients died suddenly. The HRT indices turbulence onset (TO%) and turbulence slope (TS ms/RR interval) were calculated from digital 24-hour electrocardiogram before and after 6 months of CRT. TO ≥ 0% and TS ≤ 2.5 ms/RR interval were considered abnormal.
Results: Mean TO in the entire population was 0.4 ± 1.5 before CRT, and decreased to −0.8 ± 7.0 during the 6 months of CRT (ns). TS increased significantly from 2.0 ± 1.7 at baseline, to 3.9 ± 3.1 (P < 0.05), and a significantly lower proportion of patients had abnormal HRT indices at 6 months. In contrast to the significant increase observed in responders, not significant change in TS was observed among the nonresponders.
Conclusions: During 6 months of CRT, improvements in HRT indices and a decrease in the proportion of patients with abnormal HRT were observed. CRT may have beneficial effects on baroreflex sensitivity.     

Intralipid Prolongs Survival in a Rat Model of Verapamil Toxicity

Objectives: Verapamil is a lipid-soluble calcium channel blocker with significant mortality in overdose. Previous investigators have demonstrated the benefit of lipid emulsion therapy in ameliorating toxicity from lipid-soluble agents. The authors investigated the effect of Intralipid treatment in a rat model of verapamil toxicity.
Methods: Thirty sedated Wistar rats were infused with verapamil at 37.5 mg/kg/h. Five minutes after the start of infusion, animals were treated with a bolus of either 12.4 mL/kg 20% Intralipid or 12.4 mL/kg 0.9% saline. Verapamil infusion was continued until the animals were killed. Respiratory rate, heart rate, and electrocardiography were sampled every 2.5 minutes throughout.
Results: Survival was prolonged in the Intralipid-treated group (44 ± 21 vs. 24 ± 9 minutes; p = 0.003). The median lethal dose was increased in the Intralipid group (25.7 mg/kg [95% confidence interval {CI} = 24.7 to 26.7] vs. 13.6 mg/kg [95% CI = 12.2 to 15.0]). A less marked decrease in heart rate was observed during verapamil infusion in the Intralipid-treated group (6.8 beats/min [95% CI = 8.3 to 5.2] for Intralipid vs. 10.7 beats/min [95% CI = 12.6 to 8.9] for saline; p = 0.001).
Conclusions: Intralipid treatment prolongs survival and doubles median lethal dose in a rat model of verapamil toxicity. The mechanism of action remains to be elucidated.