Complement activation is associated with poor outcome after out-of-hospital cardiac arrest.

BACKGROUND: Cardiopulmonary resuscitation after cardiac arrest initiates a whole-body ischemia-reperfusion injury, which may activate the innate immune system, including the complement system. We hypothesized that complement activation and subsequent release of soluble endothelial activation markers were associated with cerebral outcome including death. METHODS: Outcome was assessed at six months and defined by cerebral performance category scale (1-2; good outcome, 3-5; poor outcome including death) in 232 resuscitated out-of-hospital cardiac arrest patients. Plasma samples obtained at admission and day three were analysed for complement activation products C3bc, the soluble terminal complement complex (sC5b-9), and soluble CD14. Endothelial cell activation was measured by soluble markers syndecan-1, sE-selectin, thrombomodulin, and vascular cell adhesion molecule. RESULTS: Forty-nine percent of the patients had good outcome. C3bc and sC5b-9 were significantly higher at admission compared to day three (p < 0.001 for both) and in patients with poor compared to good outcome (p = 0.03 and p < 0.001, respectively). Unadjusted, higher sC5b-9 at admission was associated with poor outcome (odds ratio 1.08 (95% CI 1.01-1.14), p = 0.024). Adjusted, sC5b-9 was still associated with outcome, but the association became non-significant when time to return-of-spontaneous-circulation above 25 min was included as a covariate. Endothelial cell activation markers increased from admission to day three, but only sE-selectin and thrombomodulin were significantly higher in patients with poor versus good outcome (p = 0.004 and p = 0.03, respectively) and correlated to sCD14 and sC5b-9/C3bc, respectively. CONCLUSION: Complement system activation, reflected by sC5b-9 at admission, leading to subsequent endothelial cell activation, was associated with poor outcome in out-of-hospital cardiac arrest patients.

Health-related quality of life after out-of-hospital cardiac arrest - a five-year follow-up studyJurate Saltyte Benth.

BACKGROUND: Health-related quality of life (HRQoL) is affected after out-of-hospital cardiac arrest (OHCA), but data several years after the arrest are lacking. We assessed long-term HRQoL in OHCA survivors and how known outcome predictors impact HRQoL. METHODS: In adult OHCA survivors, HRQoL was assessed five years post arrest using Short-form 36 (SF-36), EQ-5D-3 L (EQ-5D) and Hospital Anxiety and Depression Scale (HADS) among others. Results were compared to the next of kins' estimates and to a Norwegian reference population. RESULTS: Altogether 96 survivors were included mean 5.3 (range 3.6-7.2) years after OHCA. HRQoL compared well to the reference population, except for lower score for general health with 67.2 (95%CI (62.1; 72.3) vs. 72.9 (71.9; 74.0)), p = 0.03. Younger (≤58 years) vs. older survivors scored lower for general health with mean (SD) of 62.1 (27.5) vs. 73.0 (19.5), p = 0.03, vitality (55.2 (20.5) vs. 64.6 (17.3), p = 0.02, social functioning (75.3 (28.7) vs. 94.1 (13.5), p < 0.001 and mental component summary (49.0 (9.9) vs. 55.8 (6.7), p < 0.001. They scored higher for HADS-anxiety (4.8 (3.6 vs. 2.7 (2.5), p = 0.001, and had lower EQ-5D index (0.72 (0.34) vs. 0.84 (0.19), p = 0.04. Early vs. late awakeners had higher EQ-5D index (0.82 (0.23) vs. 0.71 (0.35), p = 0.04 and lower HADS-depression scores (2.5 (2.9) vs. 3.8 (2.3), p = 0.04. Next of kin estimated HRQoL similar to the survivors' own estimates. CONCLUSIONS: HRQoL five years after OHCA was good and mainly comparable to a matched reference population. Stratified analyses revealed impaired HRQoL among younger survivors and those awakening late, mainly for mental domains.

Late awakening, prognostic factors and long-term outcome in out-of-hospital cardiac arrest - results of the prospective Norwegian Cardio-Respiratory Arrest Study (NORCAST).

BACKGROUND: Outcome prediction after out-of-hospital cardiac arrest (OHCA) may lead to withdrawal of life-sustaining therapy if the prognosis is perceived negative. Single use of uncertain prognostic tools may lead to self-fulfilling prophecies and death. We evaluated prognostic tests, blinded to clinicians and without calls for hasty outcome prediction, in a prospective study. METHODS: Comatose, sedated TTM 33-treated OHCA patients of all causes were included. Clinical-neurological/-neurophysiological/-biochemical predictors were registered. Patients were dichotomized into good/poor outcome using cerebral performance category (CPC) six months and > four years post-arrest. Prognostic tools were evaluated using false positive rates (FPR). RESULTS: We included 259 patients; 49 % and 42 % had good outcome (CPC 1-2) after median six months and 5.1 years. Unwitnessed arrest, non-shockable rhythms, and no-bystander-CPR predicted poor outcome with FPR (CI) 0.05 (0.02-0.10), 0.13 (0.08-0.21), and 0.13 (0.07-0.20), respectively. Time to awakening was median 6 (0-25) days in good outcome patients. Among patients alive with sedation withdrawal >72 h, 49 % were unconscious, of whom 32 % still obtained good outcome. Only absence of pupillary light reflexes (PLR) -and N20-responses in somato-sensory evoked potentials (SSEP), as well as increased neuron-specific enolase (NSE) later than 24 h to >80 µg/L, had FPR 0. Malignant EEG (burst suppression/epileptic activity/flat) differentiated poor/good outcome with FPR 0.05 (0.01-0.15). CONCLUSION: Time to awakening was over six days in good outcome patients. Most clinical parameters had too high FPRs for prognostication, except for absent PLR and SSEP-responses >72 h after sedation withdrawal, and increased NSE later than 24 h to >80 µg/L.

Can ventilator settings reduce the negative effects of endotracheal suctioning? Investigations in a mechanical lung model.

BACKGROUND: The insertion of suction devices through endotracheal tubes (ETTs) increases airway resistance and the subsequent suctioning may reduce airway pressures and facilitate atelectasis. The aim of this study was to investigate how airway pressures and tidal volumes change when different combinations of suction equipment and ETT sizes are used, and to what extent unfavorable effects can be ameliorated by choice of ventilator settings. METHODS: A mechanical ventilator was connected to a lung model by ETTs of 9 mm, 8 mm or 7 mm internal diameter (ID) with a pressure transducer inserted distal to the ETT. The effects of suction procedures with bronchoscope and closed catheter systems were investigated during pressure controlled ventilation (PCV) and volume controlled ventilation (VCV). In each mode, the effects of changes in inspiration:expiration (I:E) ratio, trigger sensitivity and suction pressure were examined. RESULTS: The variables that contributed most to negative model airway pressures and loss of tidal volume during suctioning were (in descending order); 1) Small-size ETTs (7-8 mm ID) combined with large diameter suction devices (14-16 Fr); 2) inverse I:E ratio ventilation (in VCV); 3) negative ventilator trigger sensitivity; and 4) strong suction pressure. The pressure changes observed distal to the ETTs were not identical to those detected by the ventilator. CONCLUSIONS: Negative model airway pressure was induced by suctioning through small-size ETTs. The most extreme pressure and volume changes were ameliorated when conventional ventilator settings were used, such as PCV mode with short inspiration time and a trigger function sensitive to flow changes.