EFFECTS OF M101-AN EXTRACELLULAR HEMOGLOBIN-APPLIED DURING CARDIOPULMONARY RESUSCITATION: AN EXPERIMENTAL RODENT STUDY.

ABSTRACT: During and immediately after cardiac arrest, cerebral oxygen delivery is impaired mainly by microthrombi and cerebral vasoconstriction. This may narrow capillaries so much that it might impede the flow of red blood cells and thus oxygen transport. The aim of this proof-of-concept study was to evaluate the effect of M101, an extracellular hemoglobin-based oxygen carrier (Hemarina SA, Morlaix, France) derived from Arenicola marina , applied during cardiac arrest in a rodent model, on markers of brain inflammation, brain damage, and regional cerebral oxygen saturation. Twenty-seven Wistar rats subjected to 6 min of asystolic cardiac arrest were infused M101 (300 mg/kg) or placebo (NaCl 0.9%) concomitantly with start of cardiopulmonary resuscitation. Brain oxygenation and five biomarkers of inflammation and brain damage (from blood, cerebrospinal fluid, and homogenates from four brain regions) were measured 8 h after return of spontaneous circulation. In these 21 different measurements, M101-treated animals were not significantly different from controls except for phospho-tau only in single cerebellum regions ( P = 0.048; ANOVA of all brain regions: P = 0.004). Arterial blood pressure increased significantly only at 4 to 8 min after return of spontaneous circulation ( P < 0.001) and acidosis decreased ( P = 0.009). While M101 applied during cardiac arrest did not significantly change inflammation or brain oxygenation, the data suggest cerebral damage reduction due to hypoxic brain injury, measured by phospho-tau. Global burden of ischemia appeared reduced because acidosis was less severe. Whether postcardiac arrest infusion of M101 improves brain oxygenation is unknown and needs to be investigated.

Hypertonic saline for fluid resuscitation in ICU patients post-cardiac surgery (HERACLES): a double-blind randomized controlled clinical trial.

PURPOSE: Recent evidence questions a liberal approach to fluid resuscitation in intensive care unit (ICU) patients. Here, we assess whether use of hypertonic saline applied as single infusion at ICU admission after cardiac surgery can reduce cumulative perioperative fluid volume. METHODS: Prospective randomized double-blind single-center clinical trial investigates effects of a single infusion of hypertonic saline (HS) versus normal saline (comparator). Primary endpoint was the cumulative amount of fluid administered in patients in the hypertonic saline versus the 0.9% saline groups (during ICU stay). Upon ICU admission, patients received a single infusion of 5 ml/kg body weight of 7.3% NaCl (or 0.9% NaCl) over 60 min. Patients undergoing cardiac surgery for elective valvular and/or coronary heart disease were included. Patients with advanced organ dysfunction, infection, and/or patients on chronic steroid medication were excluded. RESULTS: A total of 101 patients were randomized to receive the study intervention (HS n = 53, NS n = 48). Cumulative fluid intake on the ICU (primary endpoint) did not differ between the HS and the NS groups [median 3193 ml (IQR 2052-4333 ml) vs. 3345 ml (IQR 2332-5043 ml)]. Postoperative urinary output until ICU discharge was increased in HS-treated patients [median 2250 ml (IQR 1640-2690 ml) vs. 1545 ml (IQR 1087-1976 ml)], and ICU fluid balance was lower in the HS group when compared to the NS group [296 ml (IQR - 441 to 1412 ml) vs. 1137 ml (IQR 322-2660 ml)]. CONCLUSION: In a monocentric prospective double-blind randomized clinical trial, we observed that hypertonic saline did not reduce the total fluid volume administered on the ICU in critically ill cardiac surgery patients. Hypertonic saline infusion was associated with timely increase in urinary output. Variations in electrolyte and acid-base homeostasis were transient, but substantial in all patients.