Clinical detoxification of bromazolam using diazepam: a case report.

An increasing number of new psychoactive substances (NPS), such as designer benzodiazepines, are becoming available on the recreational drug market. These are new unregistered substances and thereby an attempt to evade legislation. Often there is very limited clinical information available regarding these NPS, which could result in undesirable clinical outcomes in the management of intoxications, dependencies and withdrawals following NPS use. In this case report we describe a 23-year-old woman, who was admitted to our residential addiction care facility for the detoxification of the designer benzodiazepine bromazolam. Her daily use of 6 mg bromazolam was converted to 20 mg diazepam. Although we expected a higher dose would have been needed, 20 mg was sufficient and was tapered without complications. This case report demonstrates the safe conversion of 6 mg of bromazolam to 20 mg of diazepam by combining the use of fixed-dose and symptom-triggered-dose regimens. More clinical data is necessary to formulate advisory management for the detoxification of bromazolam and other designer benzodiazepines.

Client and stakeholder perceptions of a novel, nurse practitioner-led alcohol and other drug ambulatory withdrawal service.

INTRODUCTION: Despite recommendations for ambulatory withdrawal programs appearing in many contemporary alcohol and other drug treatment guidelines, to date there have been few studies exploring such programs from client and service stakeholder perspectives. The aim of this study was to explore both individual and service stakeholder perceptions of a nurse practitioner-led ambulatory withdrawal service on the Gold Coast, Queensland, Australia. METHODS: Data were obtained from three groups: clinicians with knowledge of the service (n = 6); relatives of clients who had used the service (n = 2); and clients who had used the service (n = 10) using a Qualitative Descriptive design. Saldaña's (Saldaña, The coding manual for qualitative researchers. 2013) structural coding framework was used to analyse and code data into themes, with the study reported in accordance with the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist (Tong et al. Int J Qual Health Care 2017;19:349-57). RESULTS: Participants noted advantages of the nurse practitioner-led ambulatory withdrawal service, including rapid availability of admission to the service and a person-centred approach. Compared with other ambulatory withdrawal options, clients valued the ability to remain in their own environment, however participants suggested greater follow-up after withdrawal, with the potential of a home visiting service for greater client engagement and treatment retention. DISCUSSION AND CONCLUSIONS: Findings provide evidence to suggest that nurse practitioner-led ambulatory withdrawal services are an acceptable option for a proportion of clients who need rapid access to services when they wish to make changes to their alcohol and/or other drug use. Furthermore, they can provide person-centred care for comorbid physical and mental ill health occurring in addition to psychosocial issues associated with alcohol and/or other drug use.

Post-Overdose Extended-Release Buprenorphine Initiation Facilitated by a Partnership Between Emergency Medical Services and an Outpatient Substance Use Disorder Observation Unit.

BACKGROUND: People who experience a nonfatal opioid overdose and receive naloxone are at high risk of subsequent overdose death but experience gaps in access to medications for opioid use disorder. The immediate post-naloxone period offers an opportunity for buprenorphine initiation. Limited data indicate that buprenorphine administration by emergency medical services (EMS) after naloxone overdose reversal is safe and feasible. We describe a case in which a partnership between a low-barrier substance use disorder (SUD) observation unit and EMS allowed for buprenorphine initiation with extended-release injectable buprenorphine after naloxone overdose reversal. CASE: A man in his 40's with severe opioid use disorder and numerous prior opioid overdoses experienced overdose in the community. EMS was activated and he was successfully resuscitated with intranasal naloxone, administered by bystanders and EMS. He declined emergency department (ED) transport and consented to transport to a 24/7 SUD observation unit. The patient elected to start buprenorphine due to barriers attending opioid treatment programs daily. His largest barrier was unsheltered homelessness. His severe opioid withdrawal symptoms were successfully treated with 16/4 mg sublingual buprenorphine/naloxone and 300 mg extended-release injectable buprenorphine (XR-buprenorphine), without precipitated withdrawal. Two weeks later, he reported no interval fentanyl use. DISCUSSION: We describe the case of a patient successfully initiated onto XR-buprenorphine in the immediate post-naloxone period via a partnership between an outpatient low-barrier addiction programs and EMS. Such partnerships offer promise in expanding buprenorphine access and medication choice, particularly for the high-risk population of patients who decline ED transport.

Practices and Outcomes Associated With Sublingual Buprenorphine Use in a Critically Ill Population.

IMPORTANCE: Buprenorphine for opioid use disorder (OUD) is commonly used in the outpatient setting with increasing use in hospitalized patients. However, there is limited literature describing its use in critically ill populations. OBJECTIVES: The primary objective was to report the practices of buprenorphine prescribing among ICU teams. We also assessed the effect of a novel initiation strategy on opioid requirements in the ICU and the incidence of precipitated withdrawal. DESIGN SETTING PARTICIPANTS: Single-center, retrospective, descriptive study of patients receiving buprenorphine in the ICU. MAIN OUTCOMES AND MEASURES: The main outcome was to describe the use of buprenorphine in ICU patients through indication, initiation strategy, dosing information, and time from ICU admission to the first dose. We also detailed the incidence of precipitated withdrawal overall and the difference in opioid requirements before and after a low-dose induction strategy (buprenorphine initiated while receiving full agonist opioids [5-d titration from 150 µg to 4 mg four times daily]). RESULTS: A total of 153 patients were included. Most patients (86.3%) received buprenorphine for treatment of OUD. Of the 75 patients taking buprenorphine before admission, 46 (61%) had it restarted within 24 hours of ICU admission. Among 95 patients requiring buprenorphine induction, 57 (60%) underwent standard induction and 38 (40%) underwent low-dose induction, with only one instance of precipitated withdrawal. Median morphine milligram equivalents (MMEs) of concomitant full agonist opioids in patients completing low-dose induction decreased from 1057.5 mg to 262.5 mg in the 24 hours before initiation compared with the 24 hours after target buprenorphine dose was reached (p < 0.005). CONCLUSIONS AND RELEVANCE: Use of sublingual buprenorphine was most often in patients with OUD. Timely continuation of home buprenorphine in the ICU was suboptimal. Both standard and low-dose induction strategies appear to be safe with a low risk of precipitating withdrawal. When implemented appropriately, low-dose buprenorphine induction may lead to significant reduction in full agonist opioids in critically ill patients.

Alcohol Withdrawal Severity Measures for Identifying Patients Requiring High-Intensity Care.

OBJECTIVES: Alcohol withdrawal syndrome (AWS) may progress to require high-intensity care. Approaches to identify hospitalized patients with AWS who received higher level of care have not been previously examined. This study aimed to examine the utility of Clinical Institute Withdrawal Assessment Alcohol Revised (CIWA-Ar) for alcohol scale scores and medication doses for alcohol withdrawal management in identifying patients who received high-intensity care. DESIGN: A multicenter observational cohort study of hospitalized adults with alcohol withdrawal. SETTING: University of Chicago Medical Center and University of Wisconsin Hospital. PATIENTS: Inpatient encounters between November 2008 and February 2022 with a CIWA-Ar score greater than 0 and benzodiazepine or barbiturate administered within the first 24 hours. The primary composite outcome was patients who progressed to high-intensity care (intermediate care or ICU). INTERVENTIONS: None. MAIN RESULTS: Among the 8742 patients included in the study, 37.5% (n = 3280) progressed to high-intensity care. The odds ratio for the composite outcome increased above 1.0 when the CIWA-Ar score was 24. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) at this threshold were 0.12 (95% CI, 0.11-0.13), 0.95 (95% CI, 0.94-0.95), 0.58 (95% CI, 0.54-0.61), and 0.64 (95% CI, 0.63-0.65), respectively. The OR increased above 1.0 at a 24-hour lorazepam milligram equivalent dose cutoff of 15 mg. The sensitivity, specificity, PPV, and NPV at this threshold were 0.16 (95% CI, 0.14-0.17), 0.96 (95% CI, 0.95-0.96), 0.68 (95% CI, 0.65-0.72), and 0.65 (95% CI, 0.64-0.66), respectively. CONCLUSIONS: Neither CIWA-Ar scores nor medication dose cutoff points were effective measures for identifying patients with alcohol withdrawal who received high-intensity care. Research studies for examining outcomes in patients who deteriorate with AWS will require better methods for cohort identification.

Síndrome de abstinência em Unidade de Tratamento Intensivo Pediátrico: protocolo de revisão sistemática / Abstinence syndrome in Pediatric Intensive Care Unit: a systematic review protocol

OBJETIVO: Verificar qual o tratamento mais indicado para a prevenção e redução dos sinais e sintomas de abstinência em crianças criticamente doentes por meio de uma revisão sistemática da literatura mundial. MÉTODO: A revisão sistemática será conduzida conforme a metodologia PRISMA e Cochrane, com registro no PROSPERO, sob o número de ID CRD42021274670, nas respectivas bases de dados PubMed, LILACS, Embase, Web of Science, Cochrane, CINAHL, Cochrane Database Systematic Review e CENTRAL. As buscas serão realizadas por dois avaliadores independentes, um terceiro realizará o intermédio se necessário. Os dados serão inseridos no programa de software Zotero que irá excluir os artigos duplicados, após o material selecionado será transferido para planilha Excel em instrumento próprio. Os estudos serão classificados quanto ao seu nível de evidência, viés e fator de risco. Os resultados serão analisados e tabulados e discutidos a fim de melhor compreensão dos resultados. Se possível, serão realizadas meta-análises para os resultados agregados.

OBEJECTIVE: To verify the most appropriate treatment for the prevention and reduction of the signs and symptoms of abstinence in critically ill children through a systematic review of the world literature. METHOD: The systematic review will be conducted according to the PRISMA and Cochrane methodology, with registration at PROSPERO, under the ID number CRD42021274670, in the respective databases, PUBMed, LILACS, Embase, Web of Science, Cochrane, CINAHL, Cochrane Database Systematic Review, and CENTRAL, searches will be carried out by two independent evaluators, and a third party will perform the intermediate if necessary. The data will be entered into the Zotero software program that will delete duplicate articles after the selected material is transferred to an Excel spreadsheet on its instrument. The studies will be classified according to their level of evidence, bias, and risk factors. The results will be analyzed, tabulated, and discussed to understand the results better. If possible, meta-analyzes will be carried out for the aggregated results.

A Comparison of Injectable Diazepam and Lorazepam in the Goal-Directed Management of Severe Alcohol Withdrawal.

BACKGROUND: Benzodiazepines are the gold standard for treatment of alcohol withdrawal, yet the selection of a preferred benzodiazepine is limited due to a lack of comparative studies. OBJECTIVES: The primary objective of this study was to compare the efficacy and safety of injectable lorazepam (LZP) and diazepam (DZP) in the treatment of severe alcohol withdrawal syndrome (AWS). METHODS: Retrospective cohort study of adult patients admitted to an intensive care unit with a primary diagnosis of AWS. Subjects who received at least 12 LZP equivalent units (LEU) of injectable DZP or LZP within 24 hours of initiation of the severe AWS protocol were included. The primary outcome was time with Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) scores at goal over the first 24 hours of treatment. RESULTS: A total of 191 patients were included (DZP n = 89, LZP n = 102). Time with CIWA-Ar scores at goal during the first 24 hours was similar between groups (DZP 12 hours [interquartile range, IQR, = 9-15] vs LZP 14 hours [IQR = 10-17]), P = 0.06). At 24 hours, LEU requirement was similar (DZP 40 [IQR = 22-78] vs LZP 32 [IQR = 18-56], P = 0.05). Drug cost at 24 hours was higher in the DZP group ($204.6 [IQR = 112.53-398.97] vs $8 [IQR = 4.5-14], P < 0.01). CONCLUSION AND RELEVANCE: DZP or LZP are equally efficacious for the treatment of severe AWS. LZP may be preferred due to cost but both medications can be used interchangeably based on availability.

Current strategies for tapering psychiatric drugs: Differing recommendations, impractical doses, and other barriers.

While effective ways to prevent withdrawal symptoms from psychiatric drugs remain unclear, a highly accepted clinical approach for treatment discontinuation is to gradually reduce doses over time. The objective of this review is to gather the current strategies for tapering of psychiatric drugs described in the literature and guidelines in an attempt to identify the most promising one. Literature review and search for practice guidelines provided by government agencies and medical organizations were performed. Different strategies for tapering were found: linear tapering, hyperbolic tapering (by exponential dose reduction and pre-established dose-response curves), extended dosing, and substitution for a long half-life drug. The use of guidelines offers support for patients and prescribers, increasing the likelihood of achieving effective drug discontinuation. Nevertheless, the lack of standardization found among the guidelines makes any attempt to reduce or stop the drug very difficult for prescribers. Hyperbolic tapering by exponential dose reduction appears to be the most promising strategy for psychiatric drug discontinuation. Yet, we still face a constant challenge: how to safely obtain flexible doses for the discontinuation of drugs, particularly during the last steps in which lower doses are required. Further studies are needed to reduce the barriers associated with psychiatric drug discontinuation.

Zolpidem dependence and withdrawal. A case report of generalized seizures.

Zolpidem is a non-benzodiazepine hypnotic agent used most frequently in the treatment of insomnia, indicated for short-term use. It is not indicated for the chronic treatment of sleep disorders, despite which there is evidence in clinical practice that a large number of patients receive it for years. Although it has been described that it presents a better profile of adverse effects than benzodiazepines and that it generates a lower risk of dependence and withdrawal than these, there are significant reports of cases of dependence and withdrawal from zolpidem. A report of a case of generalized tonic-clonic seizures due to withdrawal at a dose of 300 mg per day of zolpidem is presented and a brief review of the literature is carried out.

Dependencia y abstinencia de Zolpidem. Reporte de un caso de convulsiones generalizadas

El zolpidem es un agente hipnótico no benzodiacepínico utilizado con suma frecuencia en el tratamiento del insomnio e indicado para emplearlo en el corto plazo. No está indicado para el tratamiento crónico de los trastornos del sueño, pese a lo cual se evidencia en la práctica clínica que gran cantidad de pacientes lo reciben por arios. Si bien se ha descrito que presenta un mejor perfil de efectos adversos que las benzodiacepinas y que genera menos riesgo de dependencia y abstinencia que estas, existen sendos reportes de casos de dependencia y abstinencia de zolpidem. Se presenta el reporte de un caso de convulsiones tónico-clónicas generalizadas por abstinencia a dosis de 300 mg/día de Zolpidem y se realiza una breve revisión de la literatura.

Zolpidem is a non-benzodiazepine hypnotic agent used most frequently in the treatment of insomnia, indicated for short-term use. It is not indicated for the chronic treatment of sleep disorders, despite which there is evidence in clinical practice that a large number of patients receive it for years. Although it has been described that it presents a better profile of adverse effects than benzodiazepines and that it generates a lower risk of dependence and withdrawal than these, there are significant reports of cases of dependence and withdrawal from zolpidem. A report of a case of generalized tonic-clonic seizures due to with drawal at a dose of 300 mg per day of zolpidem is presented and a brief review of the literature is carried out.

Blinded Withdrawal of Long-Term Randomized Treatment With Empagliflozin or Placebo in Patients With Heart Failure.

BACKGROUND: It is not known whether the benefits of sodium-glucose cotransporter 2 inhibitors in heart failure persist after years of therapy. METHODS: In the EMPEROR-Reduced (Empagliflozin Outcome Trials in Chronic Heart Failure With Reduced Ejection Fraction) and EMPEROR-Preserved (Empagliflozin Outcome Trials in Chronic Heart Failure With Preserved Ejection Fraction) trials, patients with heart failure were randomly assigned (double-blind) to placebo or empagliflozin 10 mg/day for a median of 16 and 26 months, respectively. At the end of the trials, 6799 patients (placebo 3381, empagliflozin 3418) were prospectively withdrawn from treatment in a blinded manner, and, of these, 3981 patients (placebo 2020, empagliflozin 1961) underwent prespecified in-person assessments after ≈30 days off treatment. RESULTS: From 90 days from the start of closeout to the end of double-blind treatment, the annualized risk of cardiovascular death or hospitalization for heart failure was lower in empagliflozin-treated patients than in placebo-treated patients (10.7 [95% CI, 9.0-12.6] versus 13.5 [95% CI, 11.5-15.6] events per 100 patient-years, respectively; hazard ratio 0.76 [95% CI, 0.60-0.96]). When the study drugs were withdrawn for ≈30 days, the annualized risk of cardiovascular death or hospitalization for heart failure increased in patients withdrawn from empagliflozin but not in those withdrawn from placebo (17.0 [95% CI, 12.6-22.1] versus 14.1 [95% CI, 10.1-18.8] events per 100 patient-years for empagliflozin and placebo, respectively). The hazard ratio for the change in risk in the patients withdrawn from empagliflozin was 1.75 (95% CI, 1.20-2.54), P=0.0034, whereas the change in the risk in patients withdrawn from placebo was not significant (hazard ratio 1.12 [95% CI, 0.76-1.66]); time period-by-treatment interaction, P=0.068. After withdrawal, the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score declined by 1.6±0.4 in patients withdrawn from empagliflozin versus placebo (P<0.0001). Furthermore, withdrawal of empagliflozin was accompanied by increases in fasting glucose, body weight, systolic blood pressure, estimated glomerular filtration rate, N-terminal pro-hormone B-type natriuretic peptide, uric acid, and serum bicarbonate and decreases in hemoglobin and hematocrit (all P<0.01). These physiological and laboratory changes were the inverse of the effects of the drug seen at the start of the trials during the initiation of treatment (≈1-3 years earlier) in the same cohort of patients. CONCLUSIONS: These observations demonstrate a persistent effect of empagliflozin in patients with heart failure even after years of treatment, which dissipated rapidly after withdrawal of the drug. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifiers: NCT03057977 and NCT03057951.

A Retrospective Comparison of the Effectiveness of Buprenorphine Versus Baclofen for Acute Opioid Withdrawal.

Background: A significant impediment to opioid cessation or dose reduction is mitigating withdrawal severity that has been shown to affect the course of opioid dependence. Current guidelines recommend the use of buprenorphine and methadone over alpha-2 adrenergic agonists. Baclofen, a GABA-B agonist, has promising results as an adjunct agent for opioid withdrawal but has not been compared to buprenorphine. This study compared the ability of buprenorphine and baclofen to mitigate acute opioid withdrawal. Methods: This was a single-center, retrospective chart review of 63 patients with diagnosed opioid use disorder that received scheduled buprenorphine or baclofen for 3 days, in addition to as-needed medications during 2 distinct time periods (pre-2017 and 2017-2020). Patients were admitted to the inpatient detoxification unit at Gateway Community Services in Jacksonville, FL. Results: The results showed that patients achieving detoxification success were 11.2 times more likely to be exposed to baclofen than buprenorphine (95% CI 3.32 - 37.83, P < .001). Completion of detoxification protocol (baclofen 63.2% vs buprenorphine 72%, P = .649) and incidence of orthostatic hypotension (15.8% versus 0%, P = .073) were not significantly different between the 2 groups. Conclusion: Patients treated with baclofen had a lower frequency of secondary medication use for acute opioid withdrawal than patients treated with buprenorphine. This raises an interesting question of whether baclofen is comparable to buprenorphine for treating opioid withdrawal. A prospective, randomized, controlled trial in a larger patient population is warranted to determine this difference.

Non-Psychosis Symptoms of Clozapine Withdrawal: a Systematic Review.

OBJECTIVE: Clozapine is a potent antipsychotic medication with a complex receptor profile. It is reserved for treatment-resistant schizophrenia. We systematically reviewed studies of non-psychosis symptoms of clozapine withdrawal. METHODS: CINAHL, Medline, PsycINFO, PubMed, and the Cochrane Database of Systematic Reviews were searched using the keywords 'clozapine,' and 'withdrawal,' or 'supersensitivity,' 'cessation,' 'rebound,' or 'discontinuation'. Studies related to non-psychosis symptoms after clozapine withdrawal were included. RESULTS: Five original studies and 63 case reports / series were included in analysis. In 195 patients included in the five original studies, approximately 20% experienced non-psychosis symptoms following discontinuation of clozapine. In 89 patients in four of the studies, 27 experienced cholinergic rebound, 13 exhibited extrapyramidal symptoms (including tardive dyskinesia), and three had catatonia. In 63 case reports / series included, 72 patients with non-psychosis symptoms were reported, which were catatonia (n=30), dystonia or dyskinesia (n=17), cholinergic rebound (n=11), serotonin syndrome (n=4), mania (n=3), insomnia (n=3), neuroleptic malignant syndrome (NMS) [n=3, one of them had both catatonia and NMS], and de novo obsessive compulsive symptoms (n=2). Restarting clozapine appeared to be the most effective treatment. CONCLUSIONS: Non-psychosis symptoms following clozapine withdrawal have important clinical implications. Clinicians should be aware of the possible presentations of symptoms to ensure early recognition and management. Further research is warranted to better characterise the prevalence, risk factors, prognosis, and optimal drug dosing for each withdrawal symptom.

Successful management of suspected propofol dependence with phenobarbital in an adult patient with COVID-19.

PURPOSE: In critically ill patients, high sedation requirements for prolonged durations are often needed to achieve ventilator synchrony, a practice that was particularly common during the early stages of the coronavirus disease 2019 (COVID-19) pandemic. We report the successful use of phenobarbital to facilitate propofol weaning after prolonged medication exposure. SUMMARY: A 64-year-old male with hypertension was admitted for the management of acute respiratory distress syndrome due to COVID-19 pneumonia. The patient received high doses of fentanyl and propofol with periods of concomitant midazolam and dexmedetomidine throughout his prolonged time on mechanical ventilation. Total days of exposure were 19 for fentanyl, 17 for propofol, 12 for midazolam, and 15 for dexmedetomidine. Upon improvement in lung function, attempts to wean the patient from propofol all failed due to symptoms such as tachypnea, tachycardia, and hypertension, with symptom resolution only upon return to the previous dose. Phenobarbital was trialed for possible propofol withdrawal syndrome, allowing for a dose reduction of 10 µg/kg/min within 2 hours of the first dose without any corresponding symptoms. The patient continued to receive intermittent doses of phenobarbital for another 36 hours until propofol was discontinued. He underwent tracheostomy shortly after weaning off all sedation and was discharged to rehab 34 days after his initial admission. CONCLUSION: Information concerning propofol withdrawal syndrome in the literature is limited. Our experience demonstrates the successful use of phenobarbital to facilitate propofol weaning after prolonged exposure.

Prevalence and Risk Factors for Iatrogenic Opioid Withdrawal in Medical Critical Care Patients.

Opioids are the mainstay of pain management and sedation in critically ill patients, which can lead to the development of physiologic tolerance and dependency. The prevalence of iatrogenic opioid withdrawal syndrome (IWS) is reported as 17-32% in the ICU; however, limited evidence exists for the medical ICU patient population. OBJECTIVES: To identify the and risk factors for IWS in adult patients admitted to critical care medicine services who received greater than or equal to 24 hours of continuous opioid infusion therapy. DESIGN SETTING AND PARTICIPANTS: A prospective, observational study was conducted in a tertiary care hospital in adult medical ICU patients. Ninety-two patients who received greater than or equal to 24 hours of continuous opioid infusions were included in the study. MAIN OUTCOMES AND MEASUREMENTS: Patients were assessed daily after opioid infusion discontinuation using the Clinical Opiate Withdrawal Scale (COWS) and the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) opioid withdrawal criteria for a maximum of 5 days. The primary outcome was the prevalence of IWS of moderate severity or greater using COWS. Secondary outcomes included the prevalence of IWS diagnosis of any severity based on COWS, the prevalence of IWS diagnosis based on a positive DSM-V score, and the identification of potential risk factors for developing IWS of any severity. RESULTS: Four hundred forty-seven patients received greater than or equal to 24 hours of continuous opioid therapy. Of these, 385 were excluded, leaving 92 patients included in the final analysis. Except for a higher prevalence of psychiatric history in the IWS-positive group, baseline characteristics were similar. Overall, 11 patients (12%) developed IWS of moderate severity or greater, based on COWS. The IWS-positive group also had longer durations of opioid infusions, higher cumulative opioid infusion doses, higher mean daily doses, and higher infusion rates at any given time. The concomitant use of dexmedetomidine (38.3 vs 15.6%, p = 0.014) and benzodiazepines (63.8 vs 37.8%, p = 0.021) during or after the opioid infusion were significantly higher in the IWS-positive group compared with the IWS-negative group. No significant differences were found between the two groups for scheduled or as needed opioids after cessation of the opioid infusion. Continuous opioid infusions greater than or equal to 72 hours and total daily dose greater than or equal to 1,200 µg were found to be independent predictors for the development of iatrogenic opioid withdrawal via logistic regression. CONCLUSIONS AND RELEVANCE: Approximately one in every eight patients receiving continuous infusion opioid for greater than 24 hours while mechanically ventilated in the medical ICU will develop IWS of moderate severity or greater; this increases to one in three patients diagnosed with DSM-V criteria or any level of IWS severity. Patients receiving opioid infusions greater than or equal to 72 hours, or a total daily fentanyl dose of greater than or equal to 1,200 µg (~ 50 µg/hr) are at a higher risk for developing IWS and should be monitored as part of clinical practice when opioid infusions are discontinued.

Clinical characteristics and outcomes using dexmedetomidine in nonintubated patients: A poison center observational study.

PURPOSE: Dexmedetomidine is a central α2 agonist commonly used on intubated patients. It is increasingly being used off-label in nonintubated agitated patients. We sought to determine the overall clinical course, adverse effects, and need for subsequent mechanical ventilation in toxicology patients after treatment with dexmedetomidine. METHODS: This was a retrospective cohort study conducted by chart review of electronic records from the Virginia Poison Control Center from January 1, 2019 to February 4, 2022. Inclusion criteria consisted of all poison center cases where dexmedetomidine was used. The primary outcome was the presence or absence of clinical improvement following dexmedetomidine use. Secondary outcomes included adverse effects, subsequent intubation, or death. RESULTS: During this study period, there were 220 cases in which dexmedetomidine was used to treat agitation. After exclusions, 70 cases were analyzed. The categories included antimuscarinic (n = 19), polysubstance (n = 16), sedative withdrawal (n = 10), unknown agitation (n = 7), sympathomimetic (n = 5), baclofen withdrawal (n = 3), unknown ingestion (n = 3), sedative/hypnotic (n = 2), antipsychotic (n = 2), hallucinogenic (n = 2), and opioid withdrawal (n = 1). Clinical improvement occurred in 62 of 70 patients (89%). There were no deaths. A total of 4 patients were intubated after starting dexmedetomidine, 2 for refractory agitation and 2 for hypoxia after aspiration. CONCLUSION: Global clinical improvement was observed in the agitated toxicology patients administered dexmedetomidine. There was one case of intubation secondary to oversedation. Dexmedetomidine could be a useful adjunctive treatment for agitated toxicologic patients but should be studied further before routinely used.

Incidence of iatrogenic withdrawal syndrome and associated factors in surgical pediatric intensive care.

BACKGROUND: Iatrogenic withdrawal syndrome (IWS) is a complication of prolonged sedation/analgesia in pediatric intensive care unit (PICU) patients. The epidemiology of IWS is poorly understood, as validated diagnostic tools are rarely used. The main objective of our study was to use the WAT-1 score to assess the incidence of IWS in our unit. The secondary objectives were to evaluate the consequences of IWS, associated factors, and management modalities. MATERIAL AND METHODS: From July 2018 to January 2019, 48 children receiving endotracheal ventilation and sedation/analgesia by continuous infusion (>48 h) of benzodiazepines and/or opioids were included. As soon as sedation/analgesia was decreased and until 72 h after its complete discontinuation, the WAT-1 score was determined every 12 h. Substitution therapy was used for 98% of patients upon opioid and/or benzodiazepine withdrawal. IWS was defined as a WAT-1 score ≥3. Factors associated with IWS were assessed by univariate analysis. RESULTS: IWS occurred in 25 (52%) patients. IWS was associated with a higher number of ventilator-associated pneumonia episodes (17 [68%] vs. one [4%]) and a longer PICU stay (13 [7; 25] vs. 9.0 [5.0; 10.5]) (p<0.001). Overall, 11 patients developed IWS after less than 5 days of sedation/analgesia. Severe head injury was associated with IWS (p = 0.03). Neither sedation discontinuation nor IWS prevention was standardized. CONCLUSION: The high incidence and adverse consequences of IWS require improved prevention. Risk groups should be defined and a standardized withdrawal protocol established. The occurrence of IWS should be monitored routinely using a validated score.

Síndrome de abstinencia asociado al uso recreativo de fentanilo: serie de dos casos / Withdrawal syndrome associated with recreational use of fentanyl: case series

El abuso de sustancias como los opioides ha venido en aumento durante la última década, siendo responsable de gran número de muertes en Estados Unidos. El consumo especialmente de fentanilo se ha convertido en una epidemia que afecta la salud pública y el bienestar socioeconómico de algunos países. Colombia no es ajena a este panorama, y en los últimos años se han descrito casos de consumo de fentanilo como droga de abuso. En este artículo se presentarán dos reportes de casos de uso de fentanilo recreativo parenteral que desarrollaron síndrome de abstinencia y requirieron manejo intrahospitalario en la ciudad de Medellín-Colombia. (AU)

The abuse of substances such as opioids has been increasing over the last decade, being responsible for a large number of deaths in the United States. The consumption, especially of fentanyl, has become an epidemic that affects public health and the socioeconomic well-being of some countries. Colombia is no stranger to this panorama; in recent years, cases of fentanyl consumption as a drug of abuse have been described. In this article, two case reports of parenteral recreational fentanyl use that developed withdrawal syndrome and required in-hospital management in the city of Medellín-Colombia will be presented. (AU)

Estratégias para manejo e prevenção da síndrome de abstinência em pacientes pediátricos críticos: revisão sistemática / Strategies for the management and prevention of withdrawal syndrome in critically ill pediatric patients: a systematic review

RESUMO Objetivo: Verificar as estratégias de prevenção e tratamento da síndrome de abstinência em unidade de terapia intensiva pediátrica. Métodos: Trata-se de revisão sistemática nas bases de dados PubMed®, Lilacs, Embase, Web of Science, Cochrane, Cinahl, Cochrane Database Systematic Review e CENTRAL. Uma estratégia de busca em três etapas foi utilizada para esta revisão. O protocolo da revisão foi aprovado no PROSPERO (CRD42021274670). Resultados: Foram incluídos na análise 12 artigos. Observou-se grande heterogeneidade entre os estudos incluídos, principalmente em se tratando de esquemas terapêuticos utilizados na sedação e na analgesia. As doses de midazolam variaram de 0,05mg/kg/hora a 0,3mg/kg/hora. A morfina também variou consideravelmente, de 10mcg/kg/hora a 30mcg/kg/hora entre os estudos. A escala mais utilizada para identificação da síndrome de abstinência, entre os 12 estudos selecionados, foi a Sophia Observational Widrawal Symptoms Scale. Em três estudos, houve diferença estatística relevante na prevenção e no manejo da síndrome de abstinência com a implantação de protocolos (p < 0,01 e p < 0,001). Conclusão: Observou-se grande variação entre o regime de sedoanalgesia utilizado entre os estudos e o método de desmame e avaliação de síndrome de abstinência. São necessários mais estudos para fornecer evidências mais robustas acerca do tratamento mais indicado para prevenção e redução dos sinais e sintomas de abstinência em crianças criticamente doentes. Registro PROSPERO:CRD 42021274670

ABSTRACT Objective: To verify strategies for the prevention and treatment of abstinence syndrome in a pediatric intensive care unit. Methods: This is a systematic review in the PubMed database®, Lilacs, Embase, Web of Science, Cochrane, Cinahl, Cochrane Database Systematic Review and CENTRAL. A three-step search strategy was used for this review, and the protocol was approved in PROSPERO (CRD42021274670). Results: Twelve articles were included in the analysis. There was great heterogeneity among the studies included, especially regarding the therapeutic regimens used for sedation and analgesia. Midazolam doses ranged from 0.05mg/kg/hour to 0.3mg/kg/hour. Morphine also varied considerably, from 10mcg/kg/hour to 30mcg/kg/hour, between studies. Among the 12 selected studies, the most commonly used scale for the identification of withdrawal symptoms was the Sophia Observational Withdrawal Symptoms Scale. In three studies, there was a statistically significant difference in the prevention and management of the withdrawal syndrome due to the implementation of different protocols (p < 0.01 and p < 0.001). Conclusion: There was great variation in the sedoanalgesia regimen used by the studies and the method of weaning and evaluation of withdrawal syndrome. More studies are needed to provide more robust evidence about the most appropriate treatment for the prevention and reduction of withdrawal signs and symptoms in critically ill children. PROSPERO register: CRD 42021274670