Iatrogenic Withdrawal Syndrome Research Articles

Management of intensive care unit withdrawal syndrome

Intensive care unit (ICU) patients frequently develop physical and psychological dependence on analgesic and sedative medications, which can lead to Iatrogenic withdrawal syndrome (IWS) upon discontinuation or tapering. The incidence of IWS in adult ICU patients varies significantly, with reported rates ranging from 12% to 100%. Identified risk factors for IWS include advanced age, obesity, medication dosage, and duration of exposure. The clinical manifestations of IWS are varied and include increased excitability of the central nervous system, gastrointestinal disturbances, and sympathetic nervous system hyperactivity. Preventive and therapeutic strategies for IWS encompass individualized medication regimens, structured withdrawal protocols, and a combination of pharmacological and non-pharmacological interventions. This review emphasizes the critical need for heightened awareness and improved management strategies to mitigate the incidence of IWS in ICU patients.

Impact of Intravenous Methadone Dosing Schedule on Iatrogenic Withdrawal Syndrome in a Pediatric Intensive Care Unit.

To compare median Sophia Observation withdrawal Symptoms scale (SOS) scores between -intravenous methadone dosing scheduled every 6 hours or every 8 hours for iatrogenic withdrawal -syndrome (IWS). This single-center, retrospective chart review evaluated patients aged 4 weeks through 18 years treated with intravenous methadone for IWS. Children admitted to the pediatric intensive care unit (PICU) of a tertiary care children's hospital between August 2017 and July 2021 and treated for IWS for at least 48 hours were eligible for inclusion. Methadone dosing schedules were compared, with a primary outcome of median Sophia Observation withdrawal Symptoms (SOS) score during the first 24 hours after cessation of continuous fentanyl infusion. Secondary outcomes included PICU and general pediatric unit lengths of stay, extubation failure rates, and mortality. Twenty patients met inclusion criteria, with 9 in the 6-hour dosing group. There was no difference in median SOS score, extubation failure, length of stay, or mortality between the 2 groups. During the first 24 hours after cessation of continuous fentanyl, there appears to be no -difference in IWS severity, as determined by bedside nurse scoring, between patients treated with -intravenous methadone every 6 hours compared with every 8 hours.

Study on Risk Factors and Receiver Operator Characteristic Curve of Iatrogenic Withdrawal Syndrome in Pediatric Intensive Care Units: A Retrospective Study

Introduction: The aims of this study were to investigate the independent risk factors associated with iatrogenic withdrawal syndrome in pediatric intensive care units (PICUs) and to establish receiver operator characteristic (ROC) curve to facilitate the diagnosis of iatrogenic withdrawal syndrome in clinical settings. Methods: Pediatric patients who received analgesic and sedative medication at a tertiary hospital in the southern Zhejiang region of China between January 2016 and December 2022 were selected for the study. Clinical case data were retrospectively analyzed to gather information including age, gender, weight, total dose of analgesic and sedative medication, total treatment duration, average maintenance dose, and other relevant parameters. Medically induced withdrawal symptom scores were assessed using the Sophia Observation Scale for Withdrawal Symptoms (SOS). Univariate and multivariate logistic regression analyses were conducted on the above indicators to identify the risk factors for iatrogenic withdrawal, and an ROC curve was constructed. Results: The study encompassed a total of 104 pediatric patients, comprising 47 patients in the SOS score ≥4 group and 57 patients in the SOS score ≤3 group. The incidence of iatrogenic withdrawal was 45.19%. Univariate analysis identified cumulative total dose of fentanyl, average daily dose of fentanyl, average daily dose of midazolam, and patient weight (p < 0.05) as factors associated with iatrogenic withdrawal syndrome. The logistic multiple regression analysis revealed that the average daily dose of fentanyl was an independent risk factor for the occurrence of iatrogenic withdrawal syndrome in critically ill children (p < 0.05). ROC curve analysis indicated an area under the curve of 0.711 (95% CI: 0.610–0.811) with sensitivity and specificity of 73.7% and 61.7%, respectively. Conclusion: The average daily maintenance dose of fentanyl holds significant clinical value in diagnosing and evaluating the prognosis of iatrogenic withdrawal syndrome and can provide a scientific foundation for enhancing sedative and analgesic management in clinical practice.

Seizures in 3 juvenile dogs after intravenous anesthetic drug withdrawal during weaning from mechanical ventilation suspected to be a sign of iatrogenic withdrawal syndrome.

To describe seizure activity in juvenile dogs successfully weaned from long-term mechanical ventilation. Three juvenile dogs (all approximately 3months old) underwent long-term mechanical ventilation with IV anesthesia for suspected noncardiogenic pulmonary edema. Within 24hours of extubation and within 10hours of discontinuing midazolam continuous infusions, all dogs experienced seizures, which is 1 sign of iatrogenic withdrawal syndrome. Each dog was treated with an anticonvulsant protocol, and none experienced seizures after being discharged. Each dog received IV anesthesia, including fentanyl, dexmedetomidine, midazolam, and propofol, during mechanical ventilation and subsequently experienced seizures after successful weaning from mechanical ventilation. Juvenile dogs may be at risk for seizures after weaning from mechanical ventilation and IV anesthesia. Neurological monitoring and further research into an appropriate weaning protocol may prove beneficial in juvenile dogs requiring prolonged anesthesia.

A systematic review of clinical practice guidelines and recommendations for the management of pain, sedation, delirium and iatrogenic withdrawal syndrome in pediatric intensive care.

This systematic review aimed to evaluate the quality of clinical practice guidelines (CPGs) and recommendations for managing pain, sedation, delirium, and iatrogenic withdrawal syndrome in pediatric intensive care (PICU). The objectives included evaluating the quality of recommendations, synthesizing recommendations, harmonizing the strength of the recommendation (SoR) and the certainty of evidence (CoE), and assessing the relevance of supporting evidence. A comprehensive search in four electronic databases (Medline, Embase.com, CINAHL and JBI EBP Database), 9 guideline repositories, and 13 professional societies was conducted to identify CPGs published from January 2010 to the end of May 2023 in any language. The quality of CPGs and recommendations was assessed using the AGREE II and AGREE-REX instruments. Thematic analysis was used to synthesize recommendations, and the GRADE SoR and CoE harmonization method was used to interpret the credibility of summary recommendations. A total of 18 CPGs and 170 recommendations were identified. Most CPGs were of medium-quality, and three were classified as high. A total of 30 summary recommendations were synthesized across each condition, focused on common management approaches. There was inconsistency in the SoRs and CoE for summary recommendations, those for assessment showed the highest consistency, the remaining were conditional, inconsistent, inconclusive, and lacked support from evidence. This systematic review provides an overview of the quality of CPGs for these four conditions in the PICU. While three CPGs achieved high-quality ratings, the overall findings reveal gaps in the evidence base of recommendations, patient and family involvement, and resources for implementation. The findings highlight the need for more rigorous and evidence-based approaches in the development and reporting of CPGs to enhance their trustworthiness. Further research is necessary to enhance the quality of recommendations for this setting. The results of this review can provide a valuable foundation for future CPG development. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=274364, PROSPERO (CRD42021274364).

Pilot Study of Immune Response and Iatrogenic Withdrawal Syndrome in Critically-Ill Children Receiving Fentanyl Infusion

Pilot Study of Immune Response and Iatrogenic Withdrawal Syndrome in Critically-Ill Children Receiving Fentanyl Infusion

Opioid, sedative, preadmission medication and iatrogenic withdrawal risk in UK adult critically ill patients: a point prevalence study

BackgroundIatrogenic withdrawal syndrome, after exposure medication known to cause withdrawal is recognised, yet under described in adult intensive care.AimTo investigate, opioid, sedation, and preadmission medication practice in critically ill adults with focus on aspects associated with iatrogenic withdrawal syndrome.MethodOne-day point prevalence study in UK intensive care units (ICUs). We collected ICU admission medication and/or substances with withdrawal potential, sedation policy, opioid and sedative use, dose, and duration.ResultsThirty-seven from 39 participating ICUs contributed data from 386 patients. The prevalence rate for parenteral opioid and sedative medication was 56.1% (212 patients). Twenty-three ICUs (59%) had no sedation/analgesia policy, and no ICUs screened for iatrogenic withdrawal. Patient admission medications with withdrawal-potential included antidepressants or antipsychotics (43, 20.3%) and nicotine (41, 19.3%). Of 212 patients, 202 (95.3%) received opioids, 163 (76.9%) sedatives and 153 (72.2%) both. Two hundred and two (95.3%) patients received opioids: 167 (82.7%) by continuous infusions and 90 (44.6%) patients for longer than 96-h. One hundred and sixty-three (76.9%) patients received sedatives: 157 (77.7%) by continuous infusions and 74 (45.4%) patients for longer than 96-h.ConclusionOpioid sedative and admission medication with iatrogenic withdrawal syndrome potential prevalence rates were high, and a high proportion of ICUs had no sedative/analgesic policies. Nearly half of patients received continuous opioids and sedatives for longer than 96-h placing them at high risk of iatrogenic withdrawal. No participating unit reported using a validated tool for iatrogenic withdrawal assessment.

A survey of pain practices in the surgical neonate. An Australasian perspective

ObjectivesThe aim of this study was to describe the current pain assessment and management practices in neonatal units providing surgical care across both Australia and New Zealand. MethodsAn electronic survey was administered to one nursing and one medical representative at each of the 15 Australian and New Zealand neonatal surgical units. ResultsAll 15 eligible units responded to the survey with a response rate of 97% (29/30 possible respondents). Dosing and titration of analgesics was a collaborative decision between nursing and medical staff (64%), with pain assessment being undertaken using a validated tool and occurring in 13 of the 15 units (87%). Morphine was the first choice of opioid employed and non-pharmacological measures for comfort were utilized in 11 units (79%). A weaning protocol was utilized in nine units (60%), with 14 units (93%) using a tool to guide management of Iatrogenic Withdrawal Syndrome. DiscussionThough the survey highlighted some variation in practice, there was considerable consistency in pain assessment and management practices across Australian and New Zealand neonatal units.

Effectiveness, quality and implementation of pain, sedation, delirium, and iatrogenic withdrawal syndrome algorithms in pediatric intensive care: a systematic review and meta-analysis.

Pain, sedation, delirium, and iatrogenic withdrawal syndrome are conditions that often coexist, algorithms can be used to assist healthcare professionals in decision making. However, a comprehensive review is lacking. This systematic review aimed to assess the effectiveness, quality, and implementation of algorithms for the management of pain, sedation, delirium, and iatrogenic withdrawal syndrome in all pediatric intensive care settings. A literature search was conducted on November 29, 2022, in PubMed, Embase, CINAHL and Cochrane Library, ProQuest Dissertations & Theses, and Google Scholar to identify algorithms implemented in pediatric intensive care and published since 2005. Three reviewers independently screened the records for inclusion, verified and extracted data. Included studies were assessed for risk of bias using the JBI checklists, and algorithm quality was assessed using the PROFILE tool (higher % = higher quality). Meta-analyses were performed to compare algorithms to usual care on various outcomes (length of stay, duration and cumulative dose of analgesics and sedatives, length of mechanical ventilation, and incidence of withdrawal). From 6,779 records, 32 studies, including 28 algorithms, were included. The majority of algorithms (68%) focused on sedation in combination with other conditions. Risk of bias was low in 28 studies. The average overall quality score of the algorithm was 54%, with 11 (39%) scoring as high quality. Four algorithms used clinical practice guidelines during development. The use of algorithms was found to be effective in reducing length of stay (intensive care and hospital), length of mechanical ventilation, duration of analgesic and sedative medications, cumulative dose of analgesics and sedatives, and incidence of withdrawal. Implementation strategies included education and distribution of materials (95%). Supportive determinants of algorithm implementation included leadership support and buy-in, staff training, and integration into electronic health records. The fidelity to algorithm varied from 8.2% to 100%. The review suggests that algorithm-based management of pain, sedation and withdrawal is more effective than usual care in pediatric intensive care settings. There is a need for more rigorous use of evidence in the development of algorithms and the provision of details on the implementation process. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021276053, PROSPERO [CRD42021276053].

International Analgesia and Sedation Weaning and Withdrawal Practices in Critically Ill Adults: The Adult Iatrogenic Withdrawal Study in the ICU.

Iatrogenic withdrawal syndrome (IWS) associated with opioid and sedative use for medical purposes has a reported high prevalence and associated morbidity. This study aimed to determine the prevalence, utilization, and characteristics of opioid and sedative weaning and IWS policies/protocols in the adult ICU population. International, multicenter, observational, point prevalence study. Adult ICUs. All patients aged 18 years and older in the ICU on the date of data collection who received parenteral opioids or sedatives in the previous 24 hours. None. ICUs selected 1 day for data collection between June 1 and September 30, 2021. Patient demographic data, opioid and sedative medication use, and weaning and IWS assessment data were collected for the previous 24 hours. The primary outcome was the proportion of patients weaned from opioids and sedatives using an institutional policy/protocol on the data collection day. There were 2,402 patients in 229 ICUs from 11 countries screened for opioid and sedative use; 1,506 (63%) patients received parenteral opioids, and/or sedatives in the previous 24 hours. There were 90 (39%) ICUs with a weaning policy/protocol which was used in 176 (12%) patients, and 23 (10%) ICUs with an IWS policy/protocol which was used in 9 (0.6%) patients. The weaning policy/protocol for 47 (52%) ICUs did not define when to initiate weaning, and the policy/protocol for 24 (27%) ICUs did not specify the degree of weaning. A weaning policy/protocol was used in 34% (176/521) and IWS policy/protocol in 9% (9/97) of patients admitted to an ICU with such a policy/protocol. Among 485 patients eligible for weaning policy/protocol utilization based on duration of opioid/sedative use initiation criterion within individual ICU policies/protocols 176 (36%) had it used, and among 54 patients on opioids and/or sedatives ≥ 72 hours, 9 (17%) had an IWS policy/protocol used by the data collection day. This international observational study found that a small proportion of ICUs use policies/protocols for opioid and sedative weaning or IWS, and even when these policies/protocols are in place, they are implemented in a small percentage of patients.

Implementation of an algorithm for tapering analgosedation reduces iatrogenic withdrawal syndrome in pediatric intensive care.

Proper analgosedation is a cornerstone in the treatment of critically ill patients in Pediatric Intensive Care Units (PICUs). Medications, such as fentanyl, morphine, and midazolam, are essential to safe and respectful care. The use of these medications over time may lead to side effects such as iatrogenic withdrawal syndrome (IWS) in the tapering phase. The aim of the study was to test an algorithm for tapering analgosedation to reduce the prevalence of IWS in two Norwegian PICUs at Oslo University Hospital. A cohort of mechanically ventilated patients from newborn to 18 years with continuous infusions of opioids and benzodiazepines for 5 days or more were included consecutively from May 2016 to December 2021. A pre- and posttest design, with an intervention phase using an algorithm for tapering analgosedation after the pretest, was used. The ICU staffs were trained in using the algorithm after the pretest. The primary outcome was a reduction in IWS. The Withdrawal Assessment Tool-1 (WAT-1) was used to identify IWS. A WAT-1 score ≥3 indicates IWS. We included 80 children, 40 in the baseline group, and 40 in the intervention group. Age and diagnosis did not differ between the groups. The prevalence of IWS was 95% versus 52.5% in the baseline group versus the intervention group, and the peak WAT-1 median was 5.0 (IQR 4-6.8) versus 3.0 (IQR 2.0-6.0) (p = .012). Based on SUM WAT-1 ≥ 3, which describes the burden over time better, we demonstrated a reduction of IWS, from a median of 15.5 (IQR 8.25-39) to a median of 3 (IQR 0-20) (p = <.001). We suggest using an algorithm for tapering analgosedation in PICUs since the prevalence of IWS was significantly lower in the intervention group in our study.

Analgesia and sedation in critically ill pediatric patients: an update from the recent guidelines and point of view

In the last decades, the advancement of knowledge in analgesia and sedation for critically ill pediatric patients has been conspicuous and relevant. Many recommendations have changed to ensure patients' comfort during their intensive care unit (ICU) stay and prevent and treat sedation-related complications, as well as improve functional recovery and clinical outcomes. The key aspects of the analgosedation management in pediatrics have been recently reviewed in two consensus-based documents. However, there remains a lot to be researched and understood. With this narrative review and authors' point of view, we aimed to summarize the new insights presented in these two documents to facilitate their interpretation and application in clinical practice, as well as to outline research priorities in the field. Conclusion:With this narrative review and authors' point of view, we aimedto summarize the new insights presented in these two documents to facilitate their interpretation andapplication in clinical practice, as well as to outline research priorities in the field. What is Known: • Critically ill pediatric patients receiving intensive care required analgesia and sedation to attenuate painful and stressful stimuli. •Optimal management of analgosedation is a challenge often burdened with complications such as tolerance, iatrogenic withdrawal syndrome, delirium, and possible adverse outcomes. What is New: •The new insights on the analgosedation treatment for critically ill pediatric patients delineated in the recent guidelines are summarized to identify strategies for changes in clinical practice. •Research gaps and potential for quality improvement projects are also highlighted.

A survey of current practices in sedation, analgesia, withdrawal, and delirium management in paediatric cardiac ICUs.

To characterise the current approach to sedation, analgesia, iatrogenic withdrawal syndrome and delirium in paediatric cardiac ICUs. A convenience sample survey of practitioners at institutions participating in the Pediatric Cardiac Critical Care Consortium conducted from September to December 2020. Paediatric cardiac ICUs. Survey responses were received from 33 of 42 institutions contacted. Screening for pain and agitation occurs commonly and frequently. A minority of responding centres (39%) have a written analgesia management protocol/guideline. A minority (42%) of centres have a written protocol for sedation. Screening for withdrawal occurs commonly, although triggers for withdrawal screening vary. Only 42% of respondents have written protocols for withdrawal management. Screening for delirium occurs "always" in 46% of responding centres, "sometimes" in 36% of centres and "never" 18%. Nine participating centres (27%) have written protocols for delirium management. Our survey identified that most responding paediatric cardiac ICUs lack a standardised approach to the management of analgesia, sedation, iatrogenic withdrawal, and delirium. Screening for pain and agitation occurs regularly, while screening for withdrawal occurs fairly frequently, and screening for delirium is notably less consistent. Only a minority of centres use written protocols or guidelines for the management of these problems. We believe that this represents an opportunity to significantly improve patient care within the paediatric cardiac ICU.

Characterization of early versus late opioid iatrogenic withdrawal syndrome in critically ill children transitioning from fentanyl -infusions to methadone.

Methadone is used to prevent opioid iatrogenic withdrawal syndrome (IWS) in children, but the optimal dose and overlap time with an opioid infusion have not been elucidated. The purpose was to compare clinical manifestations among patients who developed opioid IWS within 24 hours (early) versus ≥24 hours (late) of fentanyl discontinuation when enteral methadone was initiated. A retrospective, descriptive study. Pediatric and cardiovascular intensive care units at a tertiary care health system. Sixty-seven children received fentanyl infusions for ≥3 days and initiated on methadone prior to fentanyl discontinuation. The primary objective was to compare clinical characteristics between those with early versus late opioid IWS. Opioid IWS was defined as a Withdrawal Assessment Tool-1 score ≥3 within 5 days of fentanyl discontinuation. Secondary objectives included a comparison of time to IWS, clinical characteristics, and risk factors among patients with and without IWS. Fifty children (74.6 percent) developed opioid IWS within a median time of 3.5 hours. No differences were noted for those with and without IWS. Thirty-seven patients (74.0 percent) with IWS developed early IWS. A higher percentage of males in the late versus early group developed IWS, 100 percent versus 51.4 percent, p = 0.002. The median overlap time with methadone and fentanyl was shorter in the early versus late IWS group without reaching statistical significance, 27.5 versus 64.0 hours, p = 0.127. The majority developed opioid IWS, with most developing early IWS, despite methadone initiation. Future studies should evaluate the optimal methadone dosing and overlap time to prevent opioid IWS.

Choice and adequacy of sedation in critically ill mechanically ventilated children

Background: Sedation management is a crucial element of pediatric critical care medicine, aiming at reducing children's anxiety, distress, and oxygen demand. Prolonged administration of sedatives may result in drug tolerance and physical dependency. Abrupt discontinuation of these drugs in children may cause withdrawal symptoms. Our study aims to evaluate the choice and adequacy of sedation in ventilated children using the University of Michigan Sedation Scale score. Subjects and Methods: All the children aged between 1 and 12 years who were subjected to invasive ventilation during the time period October 2019 to June 2021 in the tertiary care pediatric intensive care unit (PICU) were included in the study. Results: Of the 35 children enrolled in the study, most of them spend the majority of their time in adequate sedation which accounts for around 87.1% of the total time of ventilation. Fentanyl and midazolam were the most frequently used drug combination. Oversedation and undersedation accounted for 7.9% and 5% of total ventilation hours, respectively. Out of 35 children, 10 (28%) developed iatrogenic withdrawal symptoms and 4 (11%) developed severe withdrawal symptoms. Conclusions: Fentanyl and midazolam were the most frequently used drug combination for attaining adequate sedation in our PICU. Irrespective of adequate sedation, no increase in the incidence of iatrogenic withdrawal syndrome, undersedation, or oversedation was noted in our study population.

813: OPIOID AND SEDATIVE USE IN ADULT ICUS: ADULT IATROGENIC WITHDRAWAL STUDY IN THE ICU (ALERT-ICU)

Introduction: Iatrogenic withdrawal syndrome (IWS) is associated with large doses and prolonged use of opioids-sedatives. This study aimed to determine current utilization patterns of opioids-sedatives in adult ICUs that may be associated with IWS. We hypothesized that cumulative doses would increase with prolonged ICU stay. Methods: We conducted an international, observational, point prevalence study on a single date between June 1 and September 30, 2021 for adult ICU patients (≥ 18 years). Demographic data, medication exposures in the preceding 24 hours, and outcomes were collected following institutional ethics approval. The primary outcome was the proportion of patients receiving continuous parenteral opioids-sedatives for ≥ 72 hours. We defined continuous use as continuous IV infusion, scheduled intermittent injections, or as needed parenteral doses with at least half of the possible doses administered in 24 hours. Outcomes were compared between patients receiving opioids-sedatives < 72 and ≥ 72 hours. Parametric and nonparametric statistical analyses were performed using IBM SPSS Statistics version 28.0.0 (Armonk, New York) according to level of measurement, data distribution and assumptions. The a priori alpha was 5%. Results: There were 1506 patients who received parenteral opioids-sedatives in 229 ICUs at 87 hospitals in 11 countries. Median ICU stay was 6 (IQR; 12) days, 31% had ARDS, and 71% were invasively mechanically ventilated. Continuous opioids were administered to 50% (647/1305), sedatives to 52% (600/1151), and both to 37% (561/1506) of patients ≥ 72-hr, with 84% receiving continuous IV infusion opioids and 98% sedatives ≥ 72-hr (p< 0.001). All median 24-hr total opioid-sedative doses were significantly greater when used ≥ 72 hr. There was no difference in opioid-sedative dose reduction in the previous 24-hr, but significantly more patients on opioids-sedatives < 72-hr received > 50% dose reductions (61% vs. 38%; p< 0.001) and had enteral opioids-sedatives initiated in the previous 24-hr (24% vs. 15%; p< 0.001). Three of 9 patients assessed had IWS, all of whom received opioids-sedatives ≥ 72-hr. Conclusions: Half of adult ICU patients receive continuous parenteral opioids-sedatives for ≥ 72-hr at higher doses than earlier in admission, which may increase the risk of IWS.

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

BackgroundIatrogenic 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 methodsFrom 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. ResultsIWS 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. ConclusionThe 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.

Risk Factors Associated With Opioid/Benzodiazepine Iatrogenic Withdrawal Syndrome in COVID-19 Acute Respiratory Distress Syndrome

Background Mechanically ventilated COVID-19 acute respiratory distress syndrome (ARDS) patients often receive deeper sedation and analgesia to maintain respiratory compliance and minimize staff exposure, which incurs greater risk of iatrogenic withdrawal syndrome (IWS) and has been associated with worse patient outcomes. Objective: To identify potential risk factors and differences in patient outcomes associated with the development of IWS in COVID-19 ARDS patients. Methods: Retrospective analysis of ventilated COVID-19 ARDS intensive care unit (ICU) patients who received continuous intravenous (IV) analgesia and sedation for ≥5 days from March 2020–May 2021. Patients were classified as IWS and non-IWS based on receipt of scheduled oral sedative/analgesic regimens after cessation of IV therapy. Risk factors were assessed in univariate analyses and multivariable modeling. Results: A total of 115 patients were included. The final multivariable model showed: (1) each additional day of IV opioid therapy was associated with an 8% increase in odds of IWS (95% CI, 1.02-1.14), (2) among sedatives, receipt of lorazepam was associated with 3 times higher odds of IWS (95% CI 1.12-8.15), and (3) each 1-point increase in Simplified Acute Physiology Score (SAPS) II was associated with a 4% reduction in odds of IWS (95% CI 0.93-0.999). Conclusion: Prolonged and high dose exposures to IV opioids and benzodiazepines should be limited when possible. Additional prospective studies are needed to identify modifiable risk factors to prevent IWS.

Four-in-One: A Comprehensive Checklist for the Assessment of Pain, Undersedation, Iatrogenic Withdrawal and Delirium in the PICU: A Delphi Study.

ObjectivesChildren's pain, undersedation, iatrogenic withdrawal syndrome and delirium often have overlapping symptoms, which makes it difficult to decide why a child in the PICU is not comfortable. Validated assessment tools for these conditions are available, but regular assessment with multiple instruments may be too time-consuming. Therefore, we aimed to develop a new holistic instrument–the mosaIC checklist–that incorporates the assessment of the four conditions.Materials and MethodsWe conducted a two-rounds international Delphi study among experts working in PICUs worldwide to find cues that in combination or separately are relevant for the four conditions.ResultsIn the first Delphi round, 38 of the 48 enrolled participants (79%) completed a questionnaire; in the second round 32 of 48 (67%). Eventually, 46 cues in eight categories (e.g., facial, vocal/verbal, body movements, sleep /behavioral state, posture/muscle tone, agitation, physiological and contextual) were found relevant. Thirty-three (72%) were considered relevant for pain, 24 for undersedation (52%), 35 for iatrogenic withdrawal syndrome (76%) and 28 (61%) for pediatric delirium. Thirteen cues (28%) were considered relevant for all four conditions; 11's (24%) for only one condition.ConclusionThis Delphi study is the first step in developing a 4-in-1 comprehensive checklist to assess pain, undersedation, iatrogenic withdrawal syndrome and delirium in a holistic manner. Further validation is needed before the checklist can be applied in practice. Application of the mosaIC checklist could help determine what condition is most likely to cause a child's discomfort–and at the same time help reduce the PICU staff's registration burden.

The complications of opioid use during and post-intensive care admission: A narrative review.

Opioids are a commonly administered analgesic medication in the intensive care unit, primarily to facilitate invasive mechanical ventilation. Consensus guidelines advocate for an opioid-first strategy for the management of acute pain in ventilated patients. As a result, these patients are potentially exposed to high opioid doses for prolonged periods, increasing the risk of adverse effects. Adverse effects relevant to these critically ill patients include delirium, intensive care unit-acquired infections, acute opioid tolerance, iatrogenic withdrawal syndrome, opioid-induced hyperalgesia, persistent opioid use, and chronic post-intensive care unit pain. Consequently, there is a challenge of optimising analgesia while minimising these adverse effects. This narrative review will discuss the characteristics of opioid use in the intensive care unit, outline the potential short-term and long-term adverse effects of opioid therapy in critically ill patients, and outline a multifaceted strategy for opioid minimisation.