Faculty Bibliography

Background: Severe baclofen toxicity (BT) can result in respiratory failure, hypotension or hypertension, bradycardia, hypothermia, seizures, coma and death. While hemodialysis (HD) is well-described in the treatment of BT in patients with end-stage renal disease (ESRD), the utility of HD in the treatment of acute BT in patients with normal renal function is less clear. Implementing HD to speed recovery after a large acute baclofen exposure is tempting, considering: a) the potential for prolonged coma and ventilator-associated morbidity, and b) baclofen's low protein binding (31%), small size (213 Da), and moderate volume of distribution (Vd =2.4 L/kg). We report the lack of efficacy of HD in a patient with an intentional baclofen overdose and normal kidney function. Case report: A 51-kg 14-year-old girl with no past medical history presented to the emergency department with hypotension, obtundation, and status epilepticus after an intentional ingestion of 1200 mg of baclofen. Her post-intubation neurologic exam was concerning for coma without any need for sedation. A 14-hour post-ingestion baclofen level was 882 ng/ml (therapeutic range 80-400 ng/ml). Urgent hemodialysis was performed due to her concerning neurologic status, with the goal of reducing her time on the ventilator. A Revaclear 300 dialyzer was used with an ultimate blood flow rate (Qb) of 300 ml/min and a dialysis fluid flow rate (Qd) of 400 ml/min. A total of three HD sessions were performed, with serum concentrations collected accordingly (Figure 1), and slow but progressive improvement in mental status. Baclofen concentrations were also systematically obtained in urine and dialysate during her hospital course. The total baclofen removed in the first three-hour HD session was 3.05 mg. The total amount of baclofen removed from urine over 24 hours on hospital day one was 42 mg, hospital day 2 was 9.2 mg, and hospital day 3 was 27.8 mg. A follow-up magnetic resonance imaging of the brain showed no evidence of anoxic brain injury. She was discharged without neurologic deficits to inpatient psychiatry on day 14. Case Discussion: There are few reports on the use of HD for acute BT in patients with normal renal function, and limited data on HD efficacy. Given the 12-fold increased quantity of baclofen recovered in urine during hospital day one in comparison to HD, the use of HD appears largely ineffective in enhancing elimination for patients with normal kidney function. Furthermore, baclofen was below the limit of detection in the dialysate on days 2 and 3. Post-HD rebound was consistent with redistribution given baclofen's larger volume of distribution. It is possible that the drug had already been distributed to tissue at the time HD was started, about 30 hours post-presentation, rendering elimination by HD ineffective.
Conclusion(s): The amount of baclofen recovered during hemodialysis is negligible in comparison to normal renal elimination in this patient with normal renal function

STUDY OBJECTIVE/OBJECTIVE:To assess the efficacy of 10mg intramuscular (IM) methadone in patients with opioid withdrawal syndrome (OWS). METHODS:This was a prospective observational, convenience sample of patients presenting to the ED with mild to moderate OWS. Evaluations included the Clinical Opiate Withdrawal Scale (COWS), Withdrawal Symptoms Scale (WSS), Altered Mental Status Scale (AMSS) and a physician assessment of the patient's WSS (MDWSS). After enrollment, 10mg of IM methadone was administered and patients were reassessed at 30min post-methadone administration. The primary outcome was the change in COWS at baseline and after methadone administration. Secondary outcomes were the differences between AMSS, and WSS post-methadone. RESULTS:Fifty-seven patients had COWS scores recorded at baseline and 30min. Fifty-six had mild to moderate OWS. The COWS improved a mean of 7.6 after methadone administration (P<0.001). The improvement was greater among patients presenting with moderate versus mild withdrawal (mean decrease=-9.1 vs. -5.5, P<0.001). Patients were more likely to self-score themselves as having withdrawal compared to MDs (93.6% vs. 76.6% respectively, P=0.027). Of the 62 patients with baseline and follow-up WSS by self-assessments, 69% improved post-methadone administration. In addition, the AMSS score remained the same or improved among 86% of cases with measurements at baseline and follow-up. CONCLUSION/CONCLUSIONS:A single IM dose of 10mg methadone in the ED reduces the severity of acute mild to moderate OWS by 30min. Larger prospective, randomized controlled, and blinded studies would be needed to confirm these results.

Historically, the clinical application of extracorporeal treatments (ECTRs), such as hemodialysis or hemoperfusion, was first intended for poisoned patients. With time, ECTRs were used almost indiscriminately to facilitate the elimination of many poisons, albeit with uncertain clinical benefit. To determine the precise role of ECTRs in poisoning situations, multiple variables need to be considered including a careful risk assessment, the poison's characteristics including toxicokinetics, alternative treatments, the patient's clinical status, and intricacies of available ECTRs, all of which are reviewed in this article. Recently, evidence-based and expert opinion-based recommendations from the EXTRIP workgroup were also published to help minimize the knowledge gap in this area.

OBJECTIVE:Although anecdotal reports suggest that intravenous lipid emulsion (ILE) therapy is effective in a large variety of overdoses, the few controlled human trials published to date yielded disappointing results. Because of potential publication biases, there are few reports concerning the failure of ILE. The primary aim of this study was to identify fatal poisoning cases in the American Association of Poison Control Centers (AAPCC) National Poison Data System (NPDS) in which ILE was administered. METHODS:We obtained an approved release of data from NPDS for years 2010-2015 in which the words "lipid," "ILE," or "fat" appeared in the narrative. Duplicate cases were excluded as were cases in which ILE was not clearly given. Case data were extracted by one author using a predetermined tool, and the information was confirmed by a second author. The timing of ILE administration was characterized into one of four categories: cardiac arrest, first line, last resort, or part of multiple therapies given simultaneously. Response to ILE and adverse events was recorded. RESULTS:Of the 826 cases retrieved from NPDS, 459 met final inclusion criteria. Over 50% of included cases involved either a calcium channel blocker or a beta-adrenergic antagonist. Of note, less than 25% of cases involved a substance for which the Lipid Emulsion Working Group found evidence to support its use. Most often, ILE was given along with multiple therapies (277 cases) or as a last resort (137 cases). In 127 cases, ILE was given during cardiac arrest. ILE was used as first line therapy in 34 cases. Response rates were reported as follows: no response (45%), unknown response (38%), transient/minimal response (7%), ROSC (7%), and immediate worsening (3%). Possible adverse reactions included: ARDS in 39 patients, lipemia causing a delay in laboratory evaluation in three cases, lipemia causing failure of a CRRT filter in two cases, worsening or new onset seizure in two cases, asystole immediately after administration in two cases, and fat embolism in one case. CONCLUSION/CONCLUSIONS:Within the Association of Poison Control Centers (AAPCC) National Poison Data System (NPDS), hundreds of cases exist in which ILE therapy was given and death occurred. In many of these cases, ILE was given prior to cardiovascular collapse. Although there is some suggestion of transient improvement in a small subset of cases, adverse effects are also reported. When taken in totality, the number of published cases of failed lipid emulsion therapy outnumbers the published instances of ILE success. Given all the uncertainty generated by case reports, the evaluation of the role and efficacy of ILE therapy in non-local anesthetic poisoning needs robust controlled clinical trials.