We Can Not Compartmentalize Our Patients! Overlapping Symptoms of Iatrogenic Withdrawal Syndrome, Pediatric Delirium, and Anticholinergic Toxidrome*
In this issue of Pediatric Critical Care Medicine, Madden et al (4) present a systematic literature review on assessment tools for IWS and PD in critically ill children. The focus of the review was on overlapping symptoms of IWS and PD. The overlapping symptoms can be classified into the following domains: motor (e.g., uncoordinated movements, tremor, and grimacing), behavior (e.g., agitation, irritability, and abnormal crying), state (e.g., sleep, time to calm, and restlessness), and psychiatric (e.g., anxiety, hallucinations, and delusions). However, they introduce a third condition; the anticholinergic toxidrome. The anticholinergic activity of a drug defines its capacity to inhibit cholinergic transmission at muscarinic receptor sites. Medication can be classified into “no risk” up to “high risk” for anticholinergic toxicity for instance antidepressants. The problem of the anticholinergic toxidrome has been studied primarily in geriatric settings, and pediatricians are not always aware of this condition. Up to seven different risk scales have been developed for use in geriatric patients but unfortunately each include different classifications for the same drugs resulting in low agreement (5, 6).
It is well known that elderly people are more at risk for polypharmacy, which generally include drugs with anticholinergic properties (7). However, critically ill children are also at risk for polypharmacy, for example, sedatives (benzodiazepines), opioids, acid reducers (ranitidine), and diuretics (furosemide) and therefore might also have high scores on an anticholinergic risk scale. The incidence of the anticholinergic toxidrome is unknown in adult ICU and PICU. Only a few pediatric case studies were found (8, 9). Symptoms of the anticholinergic toxidrome have been classified into peripheral and central ones. Peripheral symptoms have also been described in a popular way as “mad as a hatter, blind as a bat, red as a beet, hot as a hare, dry as a bone” (9). Central symptoms are similar to those of PD and IWS for instance agitation, confusion, and hallucinations (8). Therefore, assessment of the peripheral symptoms could help to differentiate anticholinergic toxidrome from PD and IWS. We propose to study the use of the skin conductance to discriminate between anticholinergic toxidrome and IWS. As with IWS, we expect increased mean skin conductance peaks, as seen in a study with Neonatal Abstinence Score babies, with anticholinergic toxidrome the opposite would be the case (10).
The review by Madden et al (4) raises a number of issues of interest for clinical practice and research. Despite the availability of validated tools for PD, an international survey revealed that delirium assessment tools are implemented in less than 30% of the PICUs (11), and we suppose that is even the case with IWS. This is surprising considering the high prevalences of IWS and PD. Or is this not surprising and due to the inability to reliably distinguish IWS and PD from each other and from pain and distress? Or are the usual suspects of problematic implementation here at stake? Examples of implementation problems are lack of knowledge, ineffective collaboration and communication between physicians and nurses, and not seeing the urgency of assessment (12).