Performance of a guideline-recommended algorithm for prognostication of poor neurological outcome after cardiac arrest

Abstract

Purpose: To assess the performance of a 4-step algorithm for neurological prognostication after cardiac arrest recommended by the European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM).

Methods: Retrospective descriptive analysis with data from the Target Temperature Management (TTM) Trial. Associations between predicted and actual neurological outcome were investigated for each step of the algorithm with results from clinical neurological examinations, neuroradiology (CT or MRI), neurophysiology (EEG and SSEP) and serum neuron-specific enolase. Patients examined with Glasgow Coma Scale Motor Score (GCS-M) on day 4 (72-96 h) post-arrest and available 6-month outcome were included. Poor outcome was defined as Cerebral Performance Category 3-5. Variations of the ERC/ESICM algorithm were explored within the same cohort.

Results: The ERC/ESICM algorithm identified poor outcome patients with 38.7% sensitivity (95% CI 33.1-44.7) and 100% specificity (95% CI 98.8-100) in a cohort of 585 patients. An alternative cut-off for serum neuron-specific enolase, an alternative EEG-classification and variations of the GCS-M had minor effects on the sensitivity without causing false positive predictions. The highest overall sensitivity, 42.5% (95% CI 36.7-48.5), was achieved when prognosticating patients irrespective of GCS-M score, with 100% specificity (95% CI 98.8-100) remaining.

Conclusion: The ERC/ESICM algorithm and all exploratory multimodal variations thereof investigated in this study predicted poor outcome without false positive predictions and with sensitivities 34.6-42.5%. Our results should be validated prospectively, preferably in patients where withdrawal of life-sustaining therapy is uncommon to exclude any confounding from self-fulfilling prophecies.

Keywords: Cardiac arrest; Coma; Guideline algorithm; Prognostic accuracy; Prognostication.

Fig. 1

This flow chart demonstrates the number of patients with 6-month outcome (n = 933), and patients excluded or included (n = 585) when assessing overall prognostic performance of the ERC/ESICM algorithm. In patients with day 4 Glasgow Coma Scale Motor Score (GCS-M), we present numbers of predicted and reported outcome when applying the current ERC/ESICM algorithm. PR & CR –/– bilaterally absent pupillary light reflexes and bilaterally absent corneal reflexes; SSEP N20 –/– bilaterally absent N20 response on short-latency somatosensory evoked potentials; NSE, elevated serum neuron-specific enolase ≥ 48 pg/mL at 48 h and/or ≥ 38 pg/mL at 72 h after cardiac arrest; EEG, unreactive status epilepticus (abundant rhythmic/periodic discharges) or unreactive burst-suppression on EEG according to ERC/ESICM criteria [; CT or MRI, generalized oedema on head computed tomography OR on magnetic resonance imaging; S. myoclonus, generalized status myoclonus ≤ 48 h after cardiac arrest; true positive, TP; predicted and reported outcome poor (CPC3–5); true negative, TN; predicted and reported outcome good (CPC1–2); false negative, FN; predicted good and reported poor. There were no false positive, FP, predictions of poor outcome in patients with reported good outcome

Fig. 2

Modified versions of Fig. 1 with exploratory alterations of the ERC/ESICM algorithm. Step 0 has been removed for clarity and is identical to Fig. 1. The figures a + b demonstrate how alterations of GCS-M as a screening criterion in Step 1 impact prognostic accuracy of the algorithm. In a, patients with day 4 GCS-M ≤ 3 are prognosticated further, and in b, patients are prognosticated irrespectable of GCS-M. In c, any ≥ 2 pathological findings in Steps 2 and 3 combined are considered indicative of poor outcome (as in the TTM2 and TAME Trials [39, 40], but we here used the ERC/ESICM definitions of pathological EEG [41] as stated in the methods section). d Represents the simplest model of multimodal prognostication, with Steps 2 and 3 combined (as in c), but without considering GCS-M in Step 1. Pathological findings were defined according to ERC/ESICM criteria [2] as described in the legend of Fig. 1 and in the methods section. True positive, TP; predicted and reported outcome poor (CPC3–5), True negative, TN; predicted and reported outcome good (CPC1–2), False negative, FN; predicted good and reported poor outcome. There were no false positive, FP, predictions of poor outcome in patients with reported good outcome. 95% confidence intervals (CI) were calculated with Wilson’s method

Fig. 3

Sensitivities and specificities of single and combined methods for prediction of poor outcome (CPC 3–5 at 6 months) in percentages, numbers of examined patients in (). The overall cohort is described in eFig. 1 and in the right column of Table 1 (n = 933). Only patients examined with a single method (bold font) or with both methods within a combination (regular font) were included therefore sensitivities of single methods may differ between combinations. Significance levels of single prognostic accuracies within combinations in Step 2/3 were calculated using the McNemars’s Test (eTables 1A + B) and are indicated by asterisks; *p < 0.05, **p < 0.01, ***p < 0.001. The absence of an asterisk (*) in Step 2/3 methods indicates that single sensitivities or specificities within combinations did not differ significantly. For example, in the combined model PR/CR and SSEP, *** signifies p < 0.001, therefore one method had significantly higher sensitivity than the other method when calculated in patients examined with both methods. GCS-M ≤ 2, Glasgow Coma Scale Motor Score on day 4 after cardiac arrest; PR/CR, bilaterally absent pupillary light reflexes AND bilaterally absent corneal reflexes