In this study, we investigated all intoxicated patients who were admitted to our medical ICU over a 15-year-long period and compared the results to a historic 5-year cohort of the 1990s. We were able to show that mixed intoxications and suicidal intent were the most common intoxication group and reason.

Patients suffering from drug and substance abuse, as well as accidental and iatrogenic intoxications constitute a substantial part of the patient collective in medical ICUs worldwide. These patients, in the acute phase, oftentimes require airway, breathing and circulatory support, need constant observation and monitoring, as well as detoxification strategies including extracorporeal poison/toxin removal [10]. The types of intoxications and poisonings vary depending on the geographical region and are influenced by diverse local health policies and laws [11, 12]. In Europe, intoxication with barbiturates and pesticides is rare nowadays, but modern designer drugs may cause intoxications with previously unknown clinical presentation [13]. Adding to the heterogeneity of intoxications, those patients may be treated in outpatient facilities, emergency departments, general wards, intermediate care units, and ICU. The admission to ICU is based on the severity of disease, but may also depend on the availability of bed capacity or regional healthcare structures. Patients therefore may be admitted to the ICU solely for monitoring purposes, but also to receive full-code intensive care treatment including mechanical ventilation, antidotes, and extracorporeal poison or toxin removal.

The median age of patients in our study was 42 years with females being significantly older than males. In the present cohort, 75% of patients were younger than 55 years of age. These results are comparable to other studies with median ages of 45 years, with 83.1% of patients being younger than 70 years [3]. In a study by Kristinsson et al., the highest incidence of intoxication was in the groups of 20- to 49-year-olds [4]. Around half of the patients requiring ICU care stated that the reason for their poisoning was suicidal intent, and one-quarter of the patients indicated recreational usage as cause for their intoxication. The rate of suicidal intent was higher among females compared to men. There was a decline of intoxication with age and a shift from recreational intent in the youngest patients to suicidal intent in the mid-range regarding age to accidental intoxication in patients at higher age. To determine possible causes for the distribution of intoxication at a younger age and to develop mental health and addiction prevention measures, further research and advocacy is necessary. The results of our study are in line with several studies in the literature that found suicide, followed by recreational intent to be the most common reasons in ICU patients admitted for intoxication [14, 15]. Liakoni et al. found that 62.0% of patients presenting to the emergency department with illicit drug consumption were 21–40 years old [16]. Schwake et al. separated the group into adverse drug reactions which showed a median of 71 years of age, and intentional intoxications resulting in a median age of 39 years [17]. In our study, recreational intoxications were roughly four times more common in men than women, in line with a study also reporting that only every fourth recreational intoxication patient is female [18].

The prevalence of common substances utilized in acute intoxications varies broadly depending on the region’s socioeconomic status, availability of drugs, and local medication prescription practice and laws, as well as mental health and addiction measures that are put in place. As there is no accepted consensus on classification, we used a classification that has previously been published using nine categories to separate toxicological intensive care patients and to display the distribution of different intoxication cases [8]. Out of the nine categories, mixed drug intoxication was the most common intoxication group among both sexes. Thereafter, men were more likely to need ICU care following ethanol use, while females needed intensive care due to intoxication with antidepressants, antipsychotics, or anticonvulsants. Females had a higher rate of pre-existing psychiatric illness in our collective, which explains the easy access to substances in this group. In comparison to the historic cohort, the rate of psychiatric diseases increased; however, we cannot exclude coding changes or increased awareness to partially account for this increase.

Interestingly, the mortality of our collective was low despite being a high-risk selection of intoxicated patients, i.e., those that needed to be admitted to the ICU. We found an ICU mortality of 4.1% with no significant differences between sexes. Furthermore, mortality has not changed over time with 4.2% in our historic comparison group from the 1990s. The most lethal intoxication group was category 6 (carbon monoxide, arsenide, and cyanide) with 14.3%. Furthermore, those patients who died in the ICU had an exorbitantly poor prognosis already when arriving at ICU, as most of these patients had prolonged pre-hospital resuscitation. Our findings are therefore in the range of other investigations that found low mortality rates in the collective of intoxicated patients in the ICU. Liisanantti et al. reported a hospital mortality of 2.5%, while Siedler et al. and McMahon et al. had an ICU mortality of 4.4% and 6.3%, respectively [2, 3, 19]. However, some studies reported frankly high numbers of mortality, but this may be due to specific intoxications in some regions (e.g., organophosphorus) or scarcity of ICU beds, as only the sickest patients are admitted. Another explanation is that in some regions emergency medical personnel must transfer patients with ongoing CPR to the hospital, while in Austria emergency physicians are deployed pre-hospitally and resuscitations in patients with a futile prognosis are often terminated on scene. As a result, the data may differ from other emergency medical services, where different CPR termination protocols are in place. The University Hospital Graz is a central hospital offering a plethora of advanced and specialized fields and is the only public HBO center in Austria. Consequently, it is the only possible destination for patients suffering from severe carbon monoxide and smoke intoxications, therefore resulting in the admission and transfer of severely ill patients from other intensive care units. Risk factors associated with mortality in multivariable analysis in our study were intubation, elevated transaminases, and creatinine as well as low pH. These findings represent factors that are inherently associated with critical illness such as intubation, liver injury, and kidney failure. These factors were associated with worse outcomes in our study, but are neither sensitive nor specific for poisonings. Other factors that may contribute to higher mortality are elapsed time from exposure to intensive care admission and dose of exposure. Furthermore, the individual substances such as carbon monoxide contribute to mortality outcomes, as mentioned above. Liisanantti et al. found cardiovascular failure as a major risk factor for succumbing in the ICU [2]. Geith et al. found non-medical substances, low GCS, and others as predictors for fatal outcomes [20]. Nevertheless, one should not be fooled by the low mortality rate, as admission to ICU is often necessary and patients receive mechanical organ replacement therapy, airway protection, and poison elimination to survive the acute phase. However, due to the heterogeneity of methods, substances, delay to admission, and many other factors, it is difficult to define, apart from obvious reasons such as mechanical ventilation, clear criteria which patients may profit the most from ICU care. Thorough documentation of pre-hospital emergency medical services on last contact time, specific toxins or blisters found at the scene, and any other information on exposure time and dose may allow in future studies to better understand the influence of these factors on outcomes. Nevertheless, it may be possible that organ damage due to hypotension and hypoxemia are the main parameters determining mortality end points.

Primary removal techniques were performed in about 30% of cases and thus to a significantly lower extent than in the 1990s (54%). Initiation of a primary removal technique is considered useful within the first hour following ingestion of a substance, but patent airway reflexes or a protected airway with an endotracheal tube is mandatory [5, 21, 22]. Therefore, the possibility of activated charcoal administration is limited in patients with altered mental status and application requires a careful benefit to risk evaluation. One strategy to enhance the efficacy of primary poison or toxin removal may be to encourage adequate early pre-hospital administration of activated charcoal. Further research in intoxications with significant enterohepatic circulation or delayed gastric passage is necessary, as these groups may benefit more from this method of detoxification and even outside of the classic 1-h window of opportunity. Duineveld et al. found in an investigation from the Netherlands that 16.1–42.5% of intoxication patients received activated charcoal [23]. In another study from Germany published in 2021, only 10.9% of patients received a primary detoxification technique in the investigated years, but only ICU data were obtained [3], whereas we investigated all available data including emergency department, emergency medical services documentation, and ICU data. In our study, females received primary removal techniques more frequently than men. In this regard, it is possible that female patients had more ingested toxins or poisons, and might seek medical assistance earlier than men allowing for  activated charcoal treatment within the recommended time window. Furthermore, as noted before, men more often had ethanol and (intravenous) street drug intoxications, which cannot be treated with activated charcoal. Changes in clinical practice and international recommendations discouraged the use of induced emesis, gastric lavage, and whole bowel irrigation [24, 25]. This is also reflected by our data, as in the historic study cohort gastric lavage was used in 97% of all patients receiving a primary detoxification method, whereas in the present study population the application of these techniques significantly declined. In addition, despite the application of gastric lavage in the historic cohort the mortality rate remained stable over time, suggesting no benefit of this previous standard technique. In the repertoire of primary detoxification methods, the role of endoscopic medication retrieval is still uncertain, but has been applied especially in the context of pharmacobezoars [26].

Secondary detoxification methods were performed in 11.7% of cases. The term forced diuresis was used frequently in the medical documentation, but when applying our more stringent criteria forced diuresis was sparsely used. The multi-dose application of activated charcoal has been discussed in recent years and is only considered helpful in a minority of intoxications such as with carbamazepine, phenobarbital, quinine, theophylline, or dapsone [22, 27]. It was used more frequently in the recent than in the historic cohort, but we can only speculate on the reasons, as there were few indications on the individual patient level compared to the frequency of utilization of multi-dose activated charcoal. There was also a shift in the applied method of extracorporeal removal from hemoperfusion, hemodialysis, and hemofiltration in the historic cohort to hemodialysis and scarcely plasma exchange in the new cohort. Extracorporeal poison or toxin removal is an integral part of intensive care therapy and a life-saving procedure in selected intoxications. In addition, intoxications are a potential reversible cause in cardiac arrest and venoarterial extracorporeal membrane oxygenation may be used as a “bridge to recovery” [28]. Antidotes, and in particular flumazenil, were used frequently and maybe even uncritically by the treating physicians in the emergency medical services, the emergency department, or the ICU. However, flumazenil should not be used liberally, as severe adverse effects such as seizures and arrhythmias have been reported, especially in mixed intoxications with tricyclic antidepressants [29]. Other studies also have found high rates of antidote usage [15, 30], but further education on appropriate antidote usage is necessary. One specific treatment strategy in poisoned patients, the high insulin euglycemic therapy or HIET, was never used in our study cohort. However, it should be noted that it may be a lifesaving therapeutic option in severe calcium channel blocker or beta-blocker overdose.

Other studies only used ICD codes to identify patients with intoxication in the ICU. This method has significant limitations, e.g., when another disease or a complication of the intoxication such as rhabdomyolysis or acute kidney injury was coded, but not the intoxication itself. In our study, we used both ICD codes and a full text search in the documentation of the patient to identify patients with potential intoxication and manually screened all documents for appropriateness. We were able to report the therapies from emergency physicians, emergency department and ICU, and obtained other necessary information from these documents not only relying on ICU documentation. We report real-life data of patients admitted to ICU; however, we did not prespecify criteria for ICU admission, as further studies are still needed to define patients that benefit significantly from ICU care. There is no clear consensus or definition for forced diuresis in literature. This global heterogenous terminology, however, makes it difficult to differentiate or compare the implementation of forced diuresis as a secondary detoxification method with other reports or publications. Interestingly, we noted that physicians used the term “forced diuresis” in their documentation heterogeneously. We did not assess for the appropriateness of the antidote application, and only investigated whether any antidote was given or not. This may result in a higher total number of antidotes given; however, the retrospective evaluation of only correct antidotes given would bias the results. The decision for application of antidotes must be performed at the bedside according to clinical assessment of the patients’ symptoms, often with little additional information available. This intrinsically leads to situations, where applied antidotes do not achieve  their intended effect. In addition, there is heterogenous use of the term antidotes in literature, as some substances, e.g., calcium gluconate or glucose, may be used for symptomatic treatment, but can also be used as a specific antidote in some poisoning. This limits the comparability between studies. Overall, a major limitation of our study is the single center design which may limit external validity.