Toxicological profile using mass-spectrometry in sudden cardiac arrest patients

Abstract Background Many drugs are known to increase the risks of ventricular arrythmias and sudden cardiac death, and current guidelines recommends collection of a blood sample at presentation for toxicological testing. To our knowledge, a broad toxicological analysis based on liquid-chromatography combined with high-resolution mass spectrometry (LC-HRMS) has not previously been performed in a resuscitated sudden cardiac arrest (SCA) cohort. Purpose We aimed to determine the qualitative and quantitative drug composition present in a well-defined SCA population by using a forensic toxicology approach for prescribed, non-prescribed, and recreational drugs, and further investigate whether these drugs were in therapeutic or toxic levels. Methods This study comprised a series of SCA patients (age 18-90 years) admitted to a cardiac intensive care unit in 2019-2020 in Denmark. Data from the SCA hospitalization was collected from the medical reports, including clinical characteristics and drugs prior to the blood sample was drawn. Drugs used during resuscitation were identified in each patient and excluded. Mass-spectrometry based toxicological analyses were performed to determine the absence or presence of any drugs and drug quantification. Results Of the 186 prospectively enrolled SCA patients (median age 62 years [IQR 54-72], 83% men), 167 (90%) had a shockable rhythm, and the majority (n=122, 66%) were caused by ischemic heart disease. We identified 92 different drugs (excluding metabolites), where each patient had a median of 2 detected drugs (IQR: 1-4). A total of 34 (18%) patients did not have any drugs detected. The most frequent drugs detected were analgesics or non-steroidal anti-inflammatory drugs (NSAID) (n=68, 37%), angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (n=45, 24%), and beta-blockers (n=42, 23%). We detected QT-prolonging drugs in two of three patients with long QT-syndrome, and in both cases the QT-prolonging drug were considered the triggering factor of SCA. Moreover, polypharmacy (≥5 drugs) was common (n=37, 20%), excluding caffeine that was detected in 184 patients (99%). The drug combinations were often analgesics/NSAID, or beta-blockers combined with other drugs. A total of 32 (17%) patients had one or more recreational drugs detected, with the most common being opioid agonists in 14 patients. Importantly, none had toxic concentrations of any drugs. Conclusion We found that 82% had at least one drug detected