Until the early 1990s, critically ill children were routinely treated without sedatives or analgesics [1, 2]. The studies conducted during this time period confirmed that sedation and analgesia in postoperative settings and pediatric intensive care units (PICUs) were essential for patient care and for reducing morbidity and mortality [1, 3]. Most PICUs currently use opioids and/or sedatives (e.g., benzodiazepines, dexmedetomidine, and propofol) for sedation and analgesia to reduce pain, stress, and anxiety in critically ill children, particularly those on mechanical ventilation or postoperative care [1].

While recent guidelines advocate lowering sedation and analgesia because numerous patients who are administered high doses of opioids and benzodiazepines via continuous intravenous infusion for prolonged periods develop cognitive morbidities [4,5,6,7,8,9]. Protracted benzodiazepine and opioid therapy frequently result in tolerance, which manifests as diminished pharmacological effects. Furthermore, withdrawal symptoms are associated with tolerance upon discontinuation [5].

IWS is a clinical reaction or phenomenon that occurs when opioid sedatives or benzodiazepines are discontinued after a long period of use. Typically, signs appear between 8 and 48 h after discontinuation, including autonomic dysregulation, gastrointestinal problems, central nervous system arousal, and motor abnormalities that can occur with the abrupt cessation or rapid tapering of the doses of these medications. [6,7,8,9,10]. Mixed IWS occurs in 7.5%–100% of pediatric patients receiving both opioids and benzodiazepines, with no mention of sequential withdrawal [4, 11, 12].

IWS is a syndrome that has been observed in many pediatric patients receiving opioids and/or sedatives for a long duration. The withdrawal was first described in adult opioid addiction literature and in neonates born to opioid-addicted mothers. However, it was first observed in pediatric patients in the 1990s [1, 13,14,15]. Arnold et al. were the first to describe this entity in neonates, noting that it could occur in infants as well [14].

Furthermore, Tobias et al. reported a protocol for preventing and treating opioid withdrawal [13].

Typically, patients who have been exposed to opioids for a long period of time suddenly develop IWS. However, it can occur within three days at high cumulative doses if drug is discontinued abruptly. According to several studies, IWS affects 35%– 64% of PICU patients [5, 8, 16]. According to an American Academy of Pediatrics clinical report, 50 to 100% of patients exposed to seven days of fentanyl therapy or a fentanyl threshold of 2 mg/kg are likely to develop withdrawal syndrome [5, 17]. IWS causes physiologic stressors such as fever, respiratory distress, tachycardia, hypertension, and feeding difficulties, as well as neurologic sequelae such as agitation, hallucinations, and seizures, which lead to prolonged hospitalization, PICU, and mechanical ventilation duration [5, 8,9,10, 18]. When reporting IWS manifestations (or any other medical condition), considering the specific age group and any potential differences in symptoms or manifestations from other age groups is important.

In pediatric patients, owing to the differences in physiology and medication use, IWS manifestations may differ from those in adults and the elderly. Therefore, a detailed description of the manifestations and any potential differences in relation to age and medication use is crucial.

For example, in pediatric patients, IWS may present as agitation, irritability, and restlessness, which could be challenging to recognize in younger children. Furthermore, medication use in pediatrics may differ from that in adults, and certain medications may be associated with an increased risk of IWS in this population.

In this vulnerable population, healthcare providers can improve their ability to recognize and manage this condition by providing a detailed description of IWS manifestations in pediatric patients and any potential differences related to age and medication use.

The reported prevalence of IWS ranges widely from 5 to 87% [12, 19], with a large prospective multicenter study in the United States involving over 1,000 patients finding a prevalence of 47% [19, 20]. For a long time, delirium has been recognized in adult ICU patients, but healthcare professionals (HCPs) haven’t recognized pediatric delirium existence before the early 2000s [21,22,23], after which several assessment tools for infants and children were validated [24,25,26]. The pediatric delirium prevalence is estimated to be 34%, ranging from 17 to 66% which depends on the studied subgroup [27]. The symptoms of pediatric delirium and IWS might overlap significantly regarding pain and sedation, [28, 29]. Dokken et al. reported that 95% of the patients had IWS based on.

Peak Withdrawal Assessment Tool Version 1 (WAT-1) scores 3 or more [30], with thiopental and propofol being the most frequently used drugs as rescue medications to treat IWS. Similar studies have found that the prevalence of IWS ranges between 47 and 77% [16, 20, 31]. Franck et al. found an IWS rate of 77% [31]. An observational multicentric study done by Amigoni et al. in 2017 observed withdrawal syndrome in 64% of PICU patients (n 1⁄4 113) who received sedation and analgesia for at least five days [5, 16]. The variation in prevalence could be attributed to a lack of universal clinical practice guidelines for preventing IWS in critically ill patients, unclear IWS signs and symptoms, and differences in medications, treatment duration, and assessment tools [5].

Investigating potential risk factors for IWS development enables healthcare providers to identify patients at risk. The incidence and influencing factors for the development of withdrawal symptoms after prolonged use of benzodiazepines or opioids in children have been extensively reported [5, 8, 32, 33]. The main risk factors associated with IWS include young age, typically less than six months, preexisting cognitive weakness, higher illness severity, cumulative dose of opioid or benzodiazepine administered, duration of treatment with these analgesics or sedatives, regular exposure for 72 h or longer, duration of extracorporeal membrane oxygenation, higher nursing workload, and lack of a sedative weaning protocol [4, 5, 10].

In the 1990s, HCPs recognized that pain assessment in hospitalized.

Children is important, which led to several observational pain assessment tools development [34], either for use for chronic pain and after major surgery, or for acute procedural pain, like prick pain. In PICU settings, 40%–65% of children cannot self-report because of mechanical ventilation and also for their young age (below the age of four) [34,35,36]. Considering the prevalence of noncommunicative kids and the requirement of quality care, it is essential that HCPs use a variety of measurement instruments to assess pain, sedation, delirium, and iatrogenic withdrawal and manage these conditions effectively [19, 37], as well as to individualize treatment and plan appropriate multimodal interventions. HCPs have access to a variety of pain and sedation assessment instruments [34, 38], and also for assessing iatrogenic withdrawal and delirium recently, [28, 34]. A recent study of 168 PICUs done in 18 countries reported that there is a wide variation in the measurement instrument use in practice regarding these four conditions [39]. Indeed, it was reported by some studies that HCPs fight to choose the appropriate assessment instrument for these four conditions [40, 41]. This could be due to the overlap of similar behavioral cue items in measurement instruments across these four conditions, or to the abundance of measurement instruments available [29, 32].

Self-report tools are the gold standard for children aged 4 and up who can communicate [38, 42]. The use of self-report tools is often not feasible in PICUs, where two-thirds of the children are under the age of four or are sedated. Therefore, after assessing pain, PICU staff members often need to assess the children’s level of sedation.

Because symptoms of distress and pain (such as hyper alertness and body movements) overlap, studies have validated some tools for both conditions. For instance, Neonatal Pain, Agitation, and Sedation Scale [43] and the COMFORT Behavior Scale. [44, 45] have both been validated for different types of pain and levels of undersedation. In addition, the COMFORT Behavior Scale also detects adequate and over sedation.

According to a 2013 systematic review, approximately 11% of PICU patients suffered from undersedation [46]. Because children admitted to a PICU often receive benzodiazepines and/or opioids, they are at risk of IWS, especially if they have been taking these drugs for more than five days. The most widely used tools for assessing IWS risk are the WAT-1 [9, 31] and the Sophia Observation withdrawal Symptoms scale (SOS) [47, 48]. The WAT-1 is an 11-item scale, with scores of 3 or higher on a scale of 0 to 12 indicating withdrawal. It was shown to have high sensitivity and specificity, as well as similar psychometric characteristics [9, 31, 49]. In addition, it has greater diagnostic accuracy, with higher areas under the receiver operating characteristic curve [9, 31, 49, 50]. Furthermore, according to Franck et al., WAT-1 is more effective in detecting opioid withdrawal symptoms than benzodiazepine withdrawal symptoms [31].

In clinical practice, four different instruments may be required to determine why a child is uncomfortable in order to decide on the first line of treatment [19]. HCPs may be unable to use four instruments on a regular basis due to time constraints, as well as a shortage of ICU nurses in most European countries, including an unknown number of nurses leaving their profession as a result of the coronavirus disease 2019 pandemic [