Do changes in SSEP amplitude over time predict the outcome of comatose survivors of cardiac arrest?

AIM: To assess if the amplitude of the N20 wave (N20Amp) of somatosensory evoked potentials (SSEPs) changes between 12-24 h and 72 h from the return of spontaneous circulation (ROSC) after cardiac arrest and if an N20Amp decrease predicts poor neurological outcome (CPC 3-5) at six months. SETTING: Retrospective analysis of the ProNeCA multicentre prognostication study dataset. (NCT03849911). METHODS: In adult comatose cardiac arrest survivors whose SSEPs were recorded at both 12-24 h and 72 h after ROSC, we measured the median N20Amp at each timepoint and the individual change in N20Amp across the two timepoints. We identified their cutoffs for predicting poor outcome with 0% false positive rate (FPR) and compared their sensitivities. RESULTS: We included 236 patients. The median [IQR] N20Amp increased from 1.90 [0.78-4.22] µV to 2.86 [1.52-5.10] µV between 12-24 h and 72 h (p = 0.0019). The N20Amp cutoff for 0% FPR increased from 0.6 µV at 12-24 h to 1.23 µV at 72 h, and its sensitivity increased from 56[48-64]% to 71[63-77]%. Between 12-24 h and 72 h, an N20Amp decrease > 53% predicted poor outcome with 0[0-5]% FPR and 26[19-35]% sensitivity. Its combination with an N20Amp < 1.23 µV at 72 h increased sensitivity by 1% to 72[64-79]%. CONCLUSION: In comatose cardiac arrest survivors, the median N20Amp and its cutoff for predicting poor neurological outcome increase between 12-24 and 72 h after ROSC. An N20Amp decrease greater than 53% between these two timepoints predicts poor outcome with 0% FPR, confirming the unfavourable prognostic signal of a low N20Amp at 72 h.

SSEP amplitude accurately predicts both good and poor neurological outcome early after cardiac arrest; a post-hoc analysis of the ProNeCA multicentre study.

AIM: To assess if, in comatose resuscitated patients, the amplitude of the N20 wave (N20amp) of somatosensory evoked potentials (SSEP) can predict 6-months neurological outcome. SETTING: Multicentre study in 13 Italian intensive care units. METHODS: The N20amp in microvolts (µV) was measured at 12 h, 24 h, and 72 h from cardiac arrest, along with pupillary reflex (PLR) and a 30-min EEG classified according to the ACNS terminology. Sensitivity and false positive rate (FPR) of N20amp alone or in combination were calculated. RESULTS: 403 patients (age 69[58-68] years) were included. At 12 h, an N20amp >3 µV predicted good neurological outcome (Cerebral Performance Categories [CPC] 1-2) with 61[50-72]% sensitivity and 11[6-18]% FPR. Combining it with a benign (continuous or nearly continuous) EEG increased sensitivity to 91[82-96]%. For poor outcome (CPC 3-5), an N20Amp ≤0.38 µV, ≤0.73 µV and ≤1.01 µV at 12 h, 24 h, and 72 h, respectively, had 0% FPR with sensitivity ranging from 61[51-69]% and 82[76-88]%. Sensitivity was higher than that of a bilaterally absent N20 at all time points. At 12 h and 24 h, a highly malignant (suppression or burst-suppression) EEG and bilaterally absent PLR achieved 0% FPR only when combined with SSEP. A combination of all three predictors yielded a 0[0-4]% FPR, with maximum sensitivity of 44[36-53]%. CONCLUSION: At 12 h from arrest, a high N20Amp predicts good outcome with high sensitivity, especially when combined with benign EEG. At 12 h and 24 h from arrest a low-voltage N20amp has a high sensitivity and is more specific than EEG or PLR for predicting poor outcome.

Neurophysiology for predicting good and poor neurological outcome at 12 and 72 h after cardiac arrest: The ProNeCA multicentre prospective study.

AIMS: To assess the accuracy of electroencephalogram (EEG) and somatosensory evoked potentials (SEPs) recorded at 12 and 72 h from resuscitation for predicting six-months neurological outcome in patients who are comatose after cardiac arrest. METHODS: Prospective multicentre prognostication study. EEG was classified according to the American Clinical Neurophysiology Society terminology. SEPs were graded according to the presence and amplitude of their cortical responses. Neurological outcome was defined as good (cerebral performance categories [CPC] 1-3) vs. poor (CPC 4-5). None of the patients underwent withdrawal of life-sustaining treatment. RESULTS: A total of 351 patients were included, of whom 134 (38%) had good neurological outcome. At 12 h, a continuous, nearly continuous and low-voltage EEG pattern predicted good neurological outcome with 71[61-80]% sensitivity, while an isoelectric EEG and a bilaterally absent/absent-pathological amplitude (AA/AP) cortical SEP pattern predicted poor neurological outcome with 14[8-21]% and 59[50-68]% sensitivity, respectively. Specificity was 100[97-100]% for all predictors. At 72 h, both an isoelectric, suppression or burst-suppression pattern on EEG and an AA/AP SEP pattern predicted poor outcome with 100[97-100]% specificity. Their sensitivities were 63[55-70]% and 66[58-74]%, respectively. When EEG and SEPs were combined, sensitivity for poor outcome prediction increased to 79%. CONCLUSIONS: In comatose resuscitated patients, EEG and SEPs predicted good and poor neurological outcome respectively, with 100% specificity as early as 12 h after cardiac arrest. At 72 h after arrest, unfavourable EEG and SEP patterns predicted poor neurological outcome with 100% specificity and high sensitivity, which further increased after their combination.

Acetyl-L-carnitine (levacecarnine) in the treatment of diabetic neuropathy. A long-term, randomised, double-blind, placebo-controlled study.

OBJECTIVE: To assess the efficacy and tolerability of acetyl-L-carnitine (levacecarnine; LAC) versus placebo in the treatment of diabetic neuropathy, mainly by evaluating the effects of treatment on electrophysiological parameters and pain symptoms. DESIGN: This was a multicentre (n = 20), randomised, double-blind, placebo-controlled, parallel-group study. PATIENTS: 333 patients meeting clinical and/or neurophysiological criteria for diabetic neuropathy were enrolled. INTERVENTIONS: Patients were randomised to treatment with LAC or placebo. LAC (or placebo) was started intramuscularly at a dosage of 1000 mg/day for 10 days and continued orally at a dosage of 2000 mg/day for the remainder of the study (355 days). MAIN OUTCOME PARAMETERS AND RESULTS: The main efficacy parameter was the effect of treatment on 6- and 12-month changes from baseline in nerve conduction velocity (NCV) and amplitude in the sensory (ulnar, sural and median) and motor (median, ulnar and peroneal) nerves. The effect of treatment on pain was also evaluated by means of a visual analogue scale (VAS). Among the 294 patients with impaired electrophysiological parameters at baseline, those treated with LAC showed a statistically significant improvement in mean NCV and amplitude compared with placebo (p < 0.01). The greatest changes in NCV (at 12 months) were observed in the sensory sural nerve (7 m/sec in the LAC group vs +1.0 m/sec in the placebo group), sensory ulnar nerve (+2.9 vs +0.1 m/sec, respectively) and motor peroneal nerve (+2.7 vs -0.2 m/sec), whereas the greatest changes in amplitude were recorded in the motor peroneal nerve (+2.2 vs +0.1 mV). After 12 months of treatment, mean VAS scores for pain were significantly reduced from baseline by 39% in LAC-treated patients (p < 0.0 vs baseline) compared with 8% in placebo recipients. LAC was well tolerated over the study period. CONCLUSIONS: LAC was effective and well tolerated in improving neurophysiological parameters and in reducing pain over a 1-year period. LAC is, therefore, a promising treatment option in patients with diabetic neuropathy.