Iatrogenic Withdrawal Syndrome Research Articles

Implementation of a Delirium Bundle for Pediatric Intensive Care Patients.

Background and ObjectiveDelirium represents the most common form of acute cerebral dysfunction in critical illness. The prevention, recognition, and treatment of delirium must become the focus of modern pediatric intensive care, as delirium can lead to increased morbidity and mortality. The aim of this study is to evaluate the impact of a delirium bundle consisting of mainly non-pharmacological measures.Material and MethodsThis is a pre-/post-implementation study in an interdisciplinary pediatric intensive care unit of a tertiary care university hospital. In the pre-implementation period, pediatric intensive care delirium was monitored using the Sophia Observation withdrawal Symptoms and Pediatric Delirium scale. After introduction of a delirium bundle consisting of non-pharmacological prevention and treatment measures a period of 4 months was interposed to train the PICU staff and ensure that the delirium bundle was implemented consistently before evaluating the effects in the post-implementation period. Data collection included prevalence of delirium and withdrawal, length of PICU stay, duration of mechanical ventilation, and cumulative dose of sedatives and analgesics.ResultsA total of 792 critically ill children aged 0–18 years were included in this study. An overall delirium prevalence of 30% was recorded in the pre-implementation group and 26% in the post-implementation group (p = 0.13). A significant reduction in the prevalence of pediatric delirium from was achieved in the subgroup of patients under 5 years of age (27.9 vs. 35.8%, p = 0.04) and in patients after surgery for congenital heart disease (28.2 vs. 39.5%, p = 0.04). Young age, length of PICU stay, and iatrogenic withdrawal syndrome were found to be risk factors for developing delirium.ConclusionsBased on a validated delirium monitoring, our study gives new information regarding the prevalence of pediatric delirium and the characteristics of intensive care patients at risk for this significant complication. Especially young patients and patients after surgery for congenital heart disease seem to benefit from the implementation of non-pharmacological delirium bundles. Based on our findings, it is important to promote change in pediatric intensive care—toward a comprehensive approach to prevent delirium in critically ill children as best as possible.

Opioid Weaning Protocol Using Morphine Compared With Nonprotocolized Methadone Associated With Decreased Dose and Duration of Opioid After Norwood Procedure.

Opioids are used to manage pain, comfort, maintain devices, and decrease oxygen consumption around Norwood palliation (NP), but in high dose and prolonged exposure, they increase risk of tolerance and iatrogenic withdrawal syndrome (IAWS). Variability in practice for IAWS prevention potentially increases opioid dose and duration. We hypothesize that protocolized weaning with morphine (MOR) versus nonprotocolized methadone (MTD) is associated with reduction in opioid exposure. A before-versus-after study of outcomes of patients weaned with protocolized MOR versus nonprotocolized MTD including subset analysis for those patients with complications postoperatively. Primary endpoints include daily, wean phase, and total morphine milligram equivalent (MMEq) dose, duration, and, secondarily, length of stay (LOS). Quaternary-care pediatric cardiac ICU. Neonates undergoing single-ventricle palliation. Introduction of IAWS prevention protocol. Analysis included 54 patients who underwent the NP in 2017-2018 including the subset analysis of 34 who had a complicated postoperative course. The total and wean phase opioid doses for the MTD group were significantly higher than that for the MOR group: 258 versus 22 and 115 versus 6 MMEq/kg; p < 0.001. Duration of opioid exposure was 63 days in the MTD group and 12 days in MOR group (p < 0.001). Subanalysis of the complicated subset also identifies higher total and wean dose for MTD group (293 vs 41 and 116 vs 7 MMEq/kg; p < 0.001) with a longer duration (65 vs 22 days; p = 0.001). Within the subset, LOS was 55% longer in the MTD group than that in the MOR group (150 vs 67 d; p = 0.01) and not different in the uncomplicated group. After complex NP, a protocolized opioid weaning using MOR versus MTD is associated with 65% shorter opioid duration, 10-fold decreased dose, and shortened LOS.

Ketamine infusions as an adjunct for sedation in critically ill children.

Limited reports have described ketamine's role as an adjunct sedative. The purpose was to describe ketamine's role as an adjunct to achieve goal sedation in mechanically ventilated children. Retrospective, descriptive study. Thirteen-bed pediatric intensive care unit (ICU) and 12-bed pediatric cardiovascular ICU. Seventy-three ketamine courses were included, representing 62 mechanically ventilated children <18 years receiving ketamine for ≥12 hours. The primary outcome was to determine the median dose and time to achieve goal sedation (80 percent of State Behavioral Scale scores between 0 and -1) based on ketamine's place in therapy as an adjunct in the sedation regimen. Secondary outcomes included a comparison of sedative dosing pre- and post-ketamine initiation between place in therapy groups and paralyzed/nonparalyzed patients, and identification of ketamine-attributed adverse drug event (ADEs) or iatrogenic withdrawal syndrome (IWS). The median age was 1.0 years (interquartile range: 0.4-4.9). Ketamine was initiated as first-line (n = 7; 9.6 percent), second-line (n = 39; 53.4 percent), third-line (n = 26; 35.6 percent), or fourth-line (n = 1; 1.4 percent) sedation. The median initial and peak doses were 0.6 mg/kg/h (0.3-0.6) and 0.9 mg/kg/h (0.9-1.2), respectively. The median dose and time to achieve goal sedation was 0.8 mg/kg/h (0.6-1.1) and 2 hours (1-7), respectively. ADEs were noted during three courses (4.1 percent) and IWS after discontinuation of one course (1.4 percent). The majority were initiated on ketamine as a second- or third-line adjunct sedative. The median initial dose was 0.6 and dose to achieve goal sedation was 0.8 mg/kg/h. Ketamine-attributed ADEs and IWS episodes were rare.

Febrile seizure secondary to opioid and benzodiazepine withdrawal in post-operative airway pediatric surgery: a case report

The sedoanalgesic drugs frequently have to be administered to relieve pain and anxiety of patients in intensive care units (ICU). An ideal agent would be rapidly metabolized, and facilitate desirable level of sedation without compromising hemodynamic and respiratory function. This makes opioids and benzodiazepines to be the most commonly prescribed drugs in intensive care. However, weaning off from these drugs may be associated with withdrawal effects. We present a case report of febrile seizure following airway pediatric surgery and opiate and benzodiazepine discontinuation. The weaning off process from these drugs should be meticulously done especially in pediatric age group to avoid subsequent complications.&#x0D; Key words: Febrile seizure; Opioids; Benzodiazepine; Withdrawal; Post-operative; Airways&#x0D; Abbreviations: PICU - Pediatric intensive care unit; IWS - Iatrogenic withdrawal syndrome&#x0D; Citation: Hehsan MR, Shukeri WFWM. Febrile seizure secondary to opioid and benzodiazepine withdrawal in post-operative airway pediatric surgery: a case report. Anaesth. pain intensive care 2021;25(6):804–806:&#x0D; DOI: 10.35975/apic.v25i6.1709&#x0D; Received: September 10, 2021, Reviewed: September 18, 2021, Accepted: October 25, 2021

Iatrogenic Withdrawal Syndrome in the Pediatric Cardiac Intensive Care Unit: Incidence, Risk Factors and Outcome.

ObjectivesCritically ill children and neonates routinely receive opioids and benzodiazepines for analgesia and sedation in the pediatric intensive care unit (PICU). Prolonged opioid therapy often leads to tolerance and is associated with iatrogenic withdrawal syndrome (IWS) when opioids and benzodiazepines are weaned or discontinued. Our aim is to study the incidence, risk factors and outcome of IWS following use of a withdrawal protocol on pediatric patients after cardiac surgery.MethodsWe prospectively included all postoperative pediatric patients who developed IWS after being assessed by the Withdrawal Assessment Tool (WAT-1) score (WAT-1 ≥3) over 9 months. Unit-based withdrawal management protocol was used. Patients’ outcome was assessed by duration to be completely off opioids & benzodiazepines, duration of ICU and hospital stay.Results432 patients were admitted during study period. Twenty-five patients (5.8%) developed IWS. The mean age and weight was 15.2 ± 31.4 months and 6.9 ± 7.7 kg respectively. 60% of the patients who developed withdrawal had previous ICU admissions with exposure to sedatives. In the IWS group the mean duration for use of fentanyl and midazolam infusions was 8.6 ± 5.1 & 9.6 ± 6 days respectively. The mean duration for completely stopping opioids and benzodiazepines was 17.2 ± 6.8 days with a mean duration of ventilation of 8.2 ± 6.8 days. The mean ICU and hospital stay for IWS patients was 26.5 ± 21.9 and 31.5 ± 21.1 days respectively. There was statistically significant difference in the mean age, and duration of use of sedatives between the patients who developed IWS and those who did not with P-value of 0.003 and < 0.0001, respectively.ConclusionWithdrawal syndrome after pediatric cardiac surgery prolongs ICU and hospital stay. Our data shows that younger age and longer duration for use of sedatives seem to be risk factors for developing withdrawal syndrome.

Safety and effectiveness of parent- or nurse-controlled analgesia in neonates: a systematic review.

The aim of this systematic review was to determine the safety and effectiveness of parent- or nurse-controlled analgesia on neonatal patient outcomes. More specifically, the objective was to determine the effect of parent- or nurse-controlled analgesia on neonatal pain scores, analgesic use, and incidence of iatrogenic withdrawal syndrome, as well as any opioid-associated adverse events. Despite recent innovations in neonatology leading to significant improvements in short- and long-term outcomes for newborns requiring intensive care, optimal management of pain and distress remains a challenge for the multidisciplinary treatment team. The inability of neonates to communicate pain easily, inconsistent practice among health professionals, insufficient analgesic prescriptions, and delays in medical reviews all impact effective pain management. Exploring the effect of parent- or nurse-controlled analgesia may identify a modality that negates these concerns and improves the pharmacological management of pain in newborns. This review considered experimental and observational studies evaluating the safety and effectiveness of parent- or nurse-controlled analgesia that included babies born at 23 weeks' gestation to four weeks post-term. The interventions considered for inclusion were any type of analgesia delivered by an infusion pump that allowed bolus dosing or a continuous analgesic infusion with bolus dosing as required. Studies using algorithms and protocols to guide timing and dosage were eligible for inclusion. Comparators included the standard management of pain for neonates in the newborn intensive care unit. A modification to the a priori protocol was made to include all neonates nursed outside of a neonatal intensive care unit to ensure all studies that examined the use of parent- or nurse-controlled analgesia in the neonatal population were included in the review. An extensive search of six major databases was conducted (CINAHL, Cochrane Library, Embase, PubMed, PsycINFO, and Web of Science). Studies published from 1997 to 2020 in English were considered for inclusion in this review. Databases searched for unpublished studies included MedNar and ProQuest Dissertations and Theses. Fourteen studies were included in this review: two randomized controlled trials, six quasi-experimental studies, one case-control study, and five case series. There was considerable heterogeneity in the interventions and study outcome measures within the studies, resulting in an inability to statistically pool results. The small sample sizes and inability to distinguish data specific to neonates in six of the studies resulted in low quality of evidence for the safety and effectiveness of parent- or nurse-controlled analgesia in neonates. However, studies reporting neonatal data demonstrated low pain scores and a trend in reduced opioid consumption when parent- or nurse-controlled analgesia was used. The use of parent- or nurse-controlled analgesia in the neonatal population has shown some effect in reducing the amount of opioid analgesia required without compromising pain relief or increasing the risk of adverse events. Due to the paucity of evidence available, certainty of the results is compromised; therefore, larger trials exploring the use of parent- or nurse-controlled analgesia in neonates and the development of nurse-led models for analgesia delivery are needed. PROSPERO CRD42018114382.

Towards Evidence-Based Weaning: a Mechanism-Based Pharmacometric Model to Characterize Iatrogenic Withdrawal Syndrome in Critically Ill Children

For the management of iatrogenic withdrawal syndrome (IWS) in children, a quantitative understanding of the dynamics of IWS of commonly used opioids and sedatives is lacking. Here, we introduce a new mechanism-based pharmacokinetic-pharmacodynamic (PKPD) modeling approach for studying IWS in pediatric clinical datasets. One thousand seven hundred eighty-two NRSwithdrawal scores of IWS severity were analyzed, which were collected from 81 children (age range: 1 month–18 years) that received opioids or sedatives by continuous infusion for 5 days or more. These data were successfully fitted with a PKPD model consisting of a plasma and a dependence compartment that well characterized the dynamics of IWS from morphine, fentanyl, and ketamine. The results suggest that (1) instead of decreasing the infusion rate by a set percentage at set intervals, it would be better to lengthen the weaning period when higher infusion rates are administered prior to weaning; (2) for fentanyl specifically, the risk of IWS might be lower when weaning with smaller dose reductions every 12 h instead of weaning with greater dose reductions every 48 h. The developed PKPD model can be used to evaluate the risk of IWS over time and the extent to which it is affected by different weaning strategies. The results yield hypotheses that could guide future clinical research on optimal weaning strategies. The mechanism-based PKPD modeling approach can be applied in other datasets to characterize the IWS dynamics of other drugs used in pediatric intensive care.Graphical abstract

Iatrogenic withdrawal syndrome frequently occurs in paediatric intensive care without algorithm for tapering of analgosedation.

Analgesics and sedatives are key elements to reduce physiological and psychological stress associated with treatment in paediatric intensive care. Prolonged drug use may induce tolerance and development of iatrogenic withdrawal syndrome (IWS) during the tapering phase. Our primary aim was to describe the prevalence of IWS among critically ill ventilated patients in two Norwegian paediatric intensive care units (PICUs), and secondary to investigate what motivated bedside nurses to administer additional drug doses. Mechanically ventilated patients (n=40) from newborn to eighteen years of age, with continuous infusions of opioids and benzodiazepines for 5days or more, were included consecutively from May 2016 to June 2018. By using Withdrawal Assessment Tool-1 (WAT-1) twice daily we recorded the prevalence of IWS. Additionally, we recorded signs and symptoms that led bedside nurses to administration extra bolus medication. Peak WAT-1 score indicated an IWS prevalence of 95% in this selected group. The first days of the tapering phase were most critical for IWS. The most frequent symptoms triggering administration of additional bolus doses were agitation/restlessness, and thiopental and propofol were the bolus drugs used most frequently. IWS affected 95% of the children having received infusions of opioids and benzodiazepines for 5days or more in PICUs without a tapering protocol for these drugs. This calls for implementation and testing of such weaning protocols.

A Systematic Review and Pooled Prevalence of Paediatric Delirium in Critically Ill Children

Abstract Introduction Paediatric Delirium (PD) is a neuropsychiatric complication that occurs during the management of children in the critical care environment (Paediatric Intensive Care (PICU) and Neonatal Intensive Care (NICU). Delirium can be classified as hypoactive (decreased responsiveness and withdrawal), hyperactive (agitation and restlessness), and mixed (combined) (1). PD can be assessed using a number of assessment tools. PD has been historically underdiagnosed or misdiagnosed, having many overlapping symptoms with other syndrome such as pain and iatrogenic withdrawal syndrome (2). An appreciation of the extent of PD would help clinicians and policy makers drive interventions to improve recognition, prevention and management of PD in clinical practice. Aim To estimate the pooled prevalence of PD using validated assessment tools, and to identify risk factors including patient-related, critical-care related and pharmacological factors. Methods A systematic search of PubMed, EMBASE and CINAHL databases was undertaken. Eligible articles included observational studies or trials that estimated a prevalence of PD in a NICU/PICU population using a validated PD assessment tool. Validated tools are the paediatric Confusion Assessment Method-ICU (pCAM-ICU), the Cornell Assessment of Pediatric Delirium (CAPD), the PreSchool Confusion Assessment Method for the ICU (psCAM-ICU), pCAM-ICU severity scale (sspCAM-ICU), and the Sophia Observation Withdrawal Symptoms scale Paediatric Delirium scale (SOS-PD) (1). Only full text studies were included. No language restrictions were applied. Two reviewers independently screened records. Data was extracted using a pre-piloted form and independently verified by another reviewer. Quality was assessed using tools from the National Institutes of Health. A pooled prevalence was calculated from the studies that estimated PD prevalence using the most commonly applied tool, the CAPD (1). Results Data from 23 observational studies describing prevalence and risk factors for PD in critically ill children were included (Figure 1). Variability in study design and outcome reporting was found. Study quality was generally good. Using the validated tools prevalence ranged from 10–66% of patients. Hypoactive delirium was the most prevalent sub-class identified. Using the 13 studies that used the CAPD tool, a pooled prevalence of 35% (27%-43% 95%CI) was calculated. Younger ages, particularly less than two years old, sicker patients, particularly those undergoing mechanical and respiratory ventilatory support were more at risk for PD. Restraints, the number of sedative medications, including the cumulative use of benzodiazepines and opioids were identified as risk factors for the development of PD. PD was associated with longer durations of mechanical ventilation, longer stays and increased costs. Data on association with increased mortality risk is limited and conflicting. Conclusion PD affects one third of critical care admissions and is resource intense. Routine assessment in clinical practice may facilitate earlier detection and management strategies. Modifiable risk factors such as the class and number of sedative and analgesic medications used may contribute to the development of PD. Early mobility and lessening use of these medications present strategies to prevent PD occurrence. Longitudinal prospective multi-institutional studies to further investigate the presentations of the different delirium subtypes and modifiable risk factors that potentially contribute to the development of PD, are required.

Maternal and iatrogenic neonatal opioid withdrawal syndrome: Differences and similarities in recognition, management, and consequences.

Opioids are potent analgesics used to manage pain in both young and old, but the increased use in the pregnant population has significant individual and societal implications. Infants dependent on opioids, either through maternal or iatrogenic exposure, undergo neonatal opioid withdrawal syndrome (NOWS), where they may experience withdrawal symptoms ranging from mild to severe. We present a detailed and original review of NOWS caused by maternal opioid exposure (mNOWS) and iatrogenic opioid intake (iNOWS). While these two entities have been assessed entirely separately, recognition and treatment of the clinical manifestations of NOWS overlap. Neonatal risk factors such as age, genetic predisposition, drug type, and clinical factors like type of opioid, cumulative dose of opioid exposure, and disease status affect the incidence of both mNOWS and iNOWS, as well as their severity. Recognition of withdrawal is dependent on clinical assessment of symptoms, and the use of clinical assessment tools designed to determine the need for pharmacotherapy. Treatment of NOWS relies on a combination of non-pharmacological therapies and pharmacological options. Long-term consequences of opioids and NOWS continue to generate controversy, with some evidence of anatomic brain changes, but conflicting animal and human clinical evidence of significant cognitive or behavioral impacts on school-age children. We highlight the current knowledge on clinically relevant recognition, treatment, and consequences of NOWS, and identify new advances in clinical management of the neonate. This review brings a unique clinical perspective and critically analyzes gaps between the clinical problem and our preclinical understanding of NOWS.

P0052 / #780: A MULTIFACETED QUALITY IMPROVEMENT INITIATIVE TO DECREASE IATROGENIC WITHDRAWAL SYNDROME IN CHILDREN NEEDING INTUBATION AND VENTILATION

Aims & Objectives: Iatrogenic withdrawal syndrome (IWS) is still a common complication in pediatric critical care. The objectives of this study were to improve the assessment of iatrogenic withdrawal syndrome (IWS) and to reduce its incidence and severity in children that were intubated and ventilated in a tertiary medical-surgical pediatric intensive care unit (PICU). Methods: This quality improvement (QI) study describes the effect of 4 interventions on IWS: a non-pharmacological bundle of measures for pain and agitation; education through simulation, newsletters, and posters; and the introduction of order sets reflecting the pain and agitation management protocol. The team monitored sedation, analgesia, and withdrawal scores biweekly, utilizing an electronic medical record report and direct observation. Interviews with frontline staff helped to optimize the interventions. Data were analyzed with process control charts, and the progress was displayed in a QI board in the PICU. Results: 293 intubated and ventilated patients, admitted from January 2018 to December 2019 were included, 211 of them assessed for IWS. The proportion of intubated patients assessed for withdrawal increased from 40% to 100%. The incidence of IWS did not change significantly with the interventions, oscillating around the mean of 83% in the high-risk population. The severity of withdrawal was reduced and sustained to 4, from 6 before the intervention. Unplanned extubation, severe pain or under sedation episodes were not affected by the interventions. Conclusions: This QI project was able to improve assessment and sustain a reduction in the severity of withdrawal, without compromising patient comfort and safety.

Dexmedetomidine and Iatrogenic Withdrawal Syndrome in Critically Ill Children.

Iatrogenic withdrawal syndrome is a well-known adverse effect of sedatives and analgesics commonly used in patients receiving mechanical ventilation in the pediatric intensive care unit, with an incidence of up to 64.6%. When standard sedative and analgesic treatment is inadequate, dexmedetomidine may be added. The effect of supplemental dexmedetomidine on iatrogenic withdrawal syndrome is unclear. To explore the potentially preventive effect of dexmedetomidine, used as a supplement to standard morphine and midazolam regimens, on the development of iatrogenic withdrawal syndrome in patients receiving mechanical ventilation in the pediatric intensive care unit. This retrospective observational study used data from patients on a 10-bed general pediatric intensive care unit. Iatrogenic withdrawal syndrome was measured using the Sophia Observation withdrawal Symptoms-scale. In a sample of 102 patients, the cumulative dose of dexmedetomidine had no preventive effect on the development of iatrogenic withdrawal syndrome (P = .19). After correction for the imbalance in the baseline characteristics between patients who did and did not receive dexmedetomidine, the cumulative dose of midazolam was found to be a significant risk factor for iatrogenic withdrawal syndrome (P < .03). In this study, supplemental dexmedetomidine had no preventive effect on iatrogenic withdrawal syndrome in patients receiving sedative treatment in the pediatric intensive care unit. The cumulative dose of midazolam was a significant risk factor for iatrogenic withdrawal syndrome.

864: Iatrogenic Withdrawal Syndrome in Children Transitioning From Fentanyl Infusion to Methadone

Hintze, Trager1; Miller, Jamie2; Neely, Stephen2; Lim, Sin Yin2; Gupta, Neha3; Johnson, Peter4 Author Information

Association of Race and Ethnicity with Sedation Management in Pediatric Intensive Care.

Rationale: Racial disparities in pain management have been previously reported for children receiving emergency care.Objectives: To determine whether patient race or ethnicity is associated with the broader goal of pain management and sedation among pediatric patients mechanically ventilated for acute respiratory failure.Methods: Planned secondary analysis of RESTORE (Randomized Evaluation of Sedation Titration for Respiratory Failure). RESTORE, a cluster-randomized clinical trial conducted in 31 U.S. pediatric intensive care units, compared protocolized sedation management (intervention arm) with usual care (control arm). Participants included 2,271 children identified as non-Hispanic white (white, n = 1,233), non-Hispanic Black (Black, n = 502), or Hispanic of any race (Hispanic, n = 536).Results: Within each treatment arm, neither opioid nor benzodiazepine selection, nor cumulative dosing, differed significantly among race and ethnicity groups. Black patients experienced fewer days with an episode of pain (compared with white patients in the control arm and with Hispanic patients in the intervention arm) and experienced less iatrogenic withdrawal syndrome (compared with white patients in either arm or with Hispanic patients in the intervention arm). The percentage of days awake and calm while intubated was not significantly different in pairwise comparisons by race and ethnicity groups in either the control arm (median: white, 75%; Black, 71%; Hispanic, 75%) or the intervention arm (white, 86%; Black, 88%; Hispanic, 85%).Conclusions: Across multiple measures, our study found scattered differences in sedation management among critically ill Black, Hispanic, and white children that did not consistently favor any group. However, racial disparities related to implicit bias cannot be completely ruled out.Clinical trial registered with clinicaltrials.gov (NCT00814099).

Strategies for the Prevention and Treatment of Iatrogenic Withdrawal from Opioids and Benzodiazepines in Critically Ill Neonates, Children and Adults: A Systematic Review of Clinical Studies.

BackgroundCritically ill patients are at high risk of iatrogenic withdrawal syndrome (IWS), due to exposure to high doses or prolonged periods of opioids and benzodiazepines.PurposeTo examine pharmacological management strategies designed to prevent and/or treat IWS from opioids and/or benzodiazepines in critically ill neonates, children and adults.MethodsWe included non-randomised studies of interventions (NRSI) and randomised controlled trials (RCTs), reporting on interventions to prevent or manage IWS in critically ill neonatal, paediatric and adult patients. Database searching included: PubMed, CINAHL, Embase, Cochrane databases, TRIP, CMA Infobase and NICE evidence. Additional grey literature was examined. Study selection and data extraction were performed in duplicate. Data collected included: population, definition of opioid, benzodiazepine or mixed IWS, its assessment and management (drug or strategy, route of administration, dosage and titration), previous drug exposures and outcomes measures. Methodological quality assessment was performed by two independent reviewers using the Cochrane risk of bias tool for RCTs and the ROBINS-I tool for NRSI. A qualitative synthesis of the results is provided. For the subset of studies evaluating multifaceted protocolised care, we meta-analysed results for 4 outcomes and examined the quality of evidence using GRADE post hoc.ResultsThirteen studies were eligible, including 10 NRSI and 3 RCTs; 11 of these included neonatal and paediatric patients exclusively. Eight studies evaluated multifaceted protocolised interventions, while 5 evaluated individual components of IWS management (e.g. clonidine or methadone at varying dosages, routes of administration and duration of tapering). IWS was measured using an appropriate tool in 6 studies. Ten studies reported upon occurrence of IWS, showing significant reductions (n = 4) or no differences (n = 6). Interventions failed to impact duration of mechanical ventilation, ICU length of stay, and adverse effects. Impact on opioid and/or benzodiazepine total doses and duration showed no differences in 4 studies, while 3 showed opioid and benzodiazepine cumulative doses were significantly reduced by 20–35% and 32–66%, and treatment durations by 1.5–11 and 19 days, respectively. Variable effects on intervention drug exposures were found. Weaning durations were reduced by 6–12 days (n = 4) for opioids and/or methadone and by 13 days (n = 1) for benzodiazepines. In contrast, two studies using interventions centred on transition to enteral routes or longer tapering durations found significant increases in intervention drug exposures. Interventions had overall non-significant effects on additional drug requirements (except for one study). Included studies were at high risk of bias, relating to selection, detection and reporting bias.ConclusionInterventions for IWS management fail to impact duration of mechanical ventilation or ICU length of stay, while effect on occurrence of IWS and drug exposures is inconsistent. Heterogeneity in the interventions used and methodological issues, including inappropriate and/or subjective identification of IWS and bias due to study design, limited the conclusions.Electronic supplementary materialThe online version of this article (10.1007/s40265-020-01338-4) contains supplementary material, which is available to authorized users.

Iatrogenic withdrawal syndrome in specialty pediatric critical care

AimTo describe the occurrence of opioid and benzodiazepine withdrawal symptoms in a cohort of pediatric intensive care unit (PICU) patients, the characteristics of this group, and patterns of withdrawal scoring observed during medication weaning. BackgroundPatients in the PICU are a complex and vulnerable population. Opioids and benzodiazepines are routinely administered in this setting. Providers must be equipped to recognize and assess symptoms of narcotic and benzodiazepine withdrawal. MethodsA retrospective chart review was conducted to describe all patients admitted to the medical intensive care unit who received continuous infusions of morphine and midazolam during a one-year period. Patient demographics, diagnosis, and presence of co-morbidities were abstracted. The number of days on continuous infusions was measured, along with Withdrawal Assessment Tool-1 (WAT-1) scores and documented symptoms that could be associated with withdrawal. WAT-1 scoring ranges from 0 to 12, a WAT-1 score of 3 or higher is considered to indicate clinically significant withdrawal symptoms. Descriptive statistics were utilized to summarize demographic and clinical variables. ResultsAmong 60 cases, patient ages ranged 5 weeks to 29 years (median 3.5 years). Eighty percent of patients had a primary respiratory diagnosis and 88.3% had one or more co-morbidities. Forty-four patients (73.3%) had symptoms consistent with withdrawal. Thirty-one percent of patients had a maximum WAT-1 score between 3 and 8. The majority of patients (55%) had a history of opioid and/or benzodiazepine exposure. ConclusionsThe information learned highlights the need for ongoing conversation and continued study of how best to assess and manage withdrawal syndrome in pediatric critical care environments.

Response.

The points raised by Dr Pektezel and collaborators are interesting and would indeed complement our pilot study. In our entry criteria, we were looking for patients who were exposed to opioids to a degree sufficient to be at risk of iatrogenic withdrawal. In this era of intensive care unit (ICU) liberation whereby analgesia is optimized, sedation is minimized, and a ventilator weaning protocol is implemented, the population most at risk of iatrogenic withdrawal in our 2 units was the trauma population. A significant portion of our patients had polytrauma and some had combined polytrauma and mild traumatic brain injury (TBI). Unfortunately, only 1 patient in our study was admitted with a nervous system disorder, representing 12% of our 8 patients who had iatrogenic withdrawal syndrome develop.1,2 No conclusion can be drawn from that sole patient.We fully agree with Dr Pektezel and collaborators that pathophysiologically, organic cerebral involvement could falsely affect the results of the Withdrawal Assessment Tool-1 (WAT-1). For this given reason, we had chosen to exclude patients with moderate and severe TBI. It remains to be determined how much mild TBI influences the validity of the WAT-1 assessment. Clearly this syndrome needs further study in a variety of critically ill adults, and the trauma population is definitely one that is at significant risk. Results of our pilot study point to a cautious approach in using the WAT-1 scale in critically ill adults. Currently, the available data are limited, and thus we are pleased that our results have raised interest in this often-unrecognized syndrome.On behalf of all authors of the original article,1

Assessment and treatment of the withdrawal syndrome in paediatric intensive care units: Systematic review.

Sedoanalgesia secondary iatrogenic withdrawal syndrome (IWS) in paediatric intensive units is frequent and its assessment is complex. Therapies are heterogeneous, and there is currently no gold standard method for diagnosis. In addition, the assessment scales validated in children are scarce. This paper aims to identify and describe both the paediatric diagnostic and assessment tools for the IWS and the treatments for the IWS in critically ill paediatric patients. A systematic review was conducted according to the PRISMA guidelines. This review included descriptive and observational studies published since 2000 that analyzed paediatric scales for the evaluation of the iatrogenic withdrawal syndrome and its treatments. The eligibility criteria included neonates, newborns, infants, pre-schoolers, and adolescents, up to age 18, who were admitted to the paediatric intensive care units with continuous infusion of hypnotics and/or opioid analgesics, and who presented signs or symptoms of deprivation related to withdrawal and prolonged infusion of sedoanalgesia. Three assessment scales were identified: Withdrawal Assessment Tool-1, Sophia Observation Withdrawal Symptoms, and Opioid and Benzodiazepine Withdrawal Score. Dexmedetomidine, methadone and clonidine were revealed as options for the treatment and prevention of the iatrogenic withdrawal syndrome. Finally, the use of phenobarbital suppressed symptoms of deprivation that are resistant to other drugs. The reviewed scales facilitate the assessment of the iatrogenic withdrawal syndrome and have a high diagnostic quality. However, its clinical use is very rare. The treatments identified in this review prevent and effectively treat this syndrome. The use of validated iatrogenic withdrawal syndrome assessment scales in paediatrics clinical practice facilitates assessment, have a high diagnostic quality, and should be encouraged, also ensuring nurses' training in their usage.

Opioid and Benzodiazepine Iatrogenic Withdrawal Syndrome in Patients in the Intensive Care Unit.

Iatrogenic withdrawal syndrome is an increasingly recognized issue among adult patients in the intensive care unit. The prolonged use of opioids and benzodiazepines during the intensive care unit stay and preexisting disorders associated with their use put patients at risk of developing iatrogenic withdrawal syndrome. Although research to date is scant regarding iatrogenic withdrawal syndrome in adult patients in the intensive care unit, it is important to recognize and adequately manage iatrogenic withdrawal syndrome in order to prevent possible negative outcomes during and after a patient's intensive care unit stay. This article discusses in depth 8 studies of iatrogenic withdrawal syndrome among adult patients in the intensive care unit. It also addresses important aspects of opioid and benzodiazepine iatrogenic withdrawal syndrome, including prevalence, risk factors, and assessment and considers its prevention and management.

Implementation of an opioid weaning protocol to improve pain management, and to prevent or decrease iatrogenic withdrawal syndrome in the neonatal intensive care.

The aim of this evidence implementation project was to improve pain assessment and management of the neonate receiving an opioid infusion, and to prevent or decrease the incidence of iatrogenic withdrawal syndrome (IWS). The current project was carried out in two intensive care areas of a 79 bed tertiary Neonatal Unit in Australia. A pre/postaudit design was utilized. Patient charts were reviewed to collect baseline audit data on pain assessments and titration of opioids. A weaning protocol was developed and implemented along with targeted staff education to align current practice with best practice recommendations. A postimplementation audit was then conducted to evaluate changes in practice. A total of 32 charts (13 pre/19 post) were reviewed to evaluate pain assessment, titration of opioids, and the identification of any signs and symptoms of IWS. The results demonstrated an improvement in the completion of pain assessments by 34%, and 100% compliance to withdrawal assessment following the introduction of an IWS assessment tool. For neonates receiving analgesics for less than 4 days, adherence to the weaning schedule occurred in 75%. No clinical signs of IWS were seen in this cohort. For neonates receiving analgesics for greater than 4 days, adherence to the weaning schedule occurred in only 55%. Of those neonates where the protocol was not followed, 67% developed clinical signs of IWS. Although this project demonstrated improvements in pain assessment and the identification of IWS, lack of adherence to the pain management policy and weaning tool has increased awareness of the importance of collaboration within the multidisciplinary team to improve outcomes. Several barriers were identified prior to implementation and various methods were employed to overcome these. Despite this, consistency of practice and change-management remain a challenge in clinical care.