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Fluid therapy in neurointensive care patients: ESICM consensus and clinical practice recommendations.

Oddo M, Poole D, Helbok R et al.
Intensive Care Med. 2018;44:449-463.

The European Society of Intensive Care Medicine (ESICM) recently published a consensus statement and clinical recommendations regarding the fluid management of neuro-intensive care patients (NIC), including comatose (GCS < 9) patients with severe traumatic brain injury (TBI), high-grade aneurysmal subarachnoid hemorrhage (SAH), severe arterial ischemic stroke (AIS) or intracerebral hemorrhage (ICH). Regarding the composition of fluids, recommendations of varying strengths are summarized as follows:

• Isotonic crystalloids as the preferred fluid for maintenance and initial resuscitation of hemodynamic instability in NIC patients
• Hypotonic crystalloids and hypertonic sodium chloride, as well as colloids, including low- and high-concentration albumin are not recommended as maintenance or initial resuscitation fluid in hypotension

Recommendations regarding the hemodynamic guidance of optimization of fluid therapy include:

• Consideration of arterial blood pressure and fluid balance as the main end points of fluid management, and integration of variables such as cardiac output, SvO2, blood lactate, urinary output; central venous pressure is not recommended as the sole or safety end point.
• Weak suggestion for normovolemia as the target for fluid replacement and against restrictive fluid strategy in NIC patients although no specific comment is made regarding these suggestions in patients with elevated ICP.

In elevated ICP, the fluid management recommendations are:

• The use of mannitol or hypertonic saline solution for reducing ICP
• The trigger for starting osmotherapy: the combination of neurological worsening (defined as a decrease of 2 points of the GCS motor score, or loss of pupillary reactivity or asymmetry, or deterioration of head CT findings) and ICP > 25 mmHg (strong recommendation); ICP > 25 mmHg independent of other variables (weak recommendation).
• Measurement of ICP response and serum osmolarity and electrolytes to reduce side effects of osmotherapy, as well as impact on arterial blood pressure and fluid balance as secondary variables.

Limited recommendations are made regarding the endpoints of fluid management of SAH patients with delayed cerebral ischemia

• The main endpoints to be used are arterial blood pressure and reversal of neurological deficit.
• The secondary endpoints suggested are transcranial Doppler cerebral blood flow velocities, improvements of cerebral perfusion and reduction of mean transit time on CT perfusion

A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest.

Perkins GD, Ji C, Deakin CD et al; PARAMEDIC2 Collaborators.
N Engl J Med. 2018;379:711-721.

This large multicenter, randomized placebo-controlled, double-blind trial of epinephrine vs saline in pre-hospital cardiac arrest aims to elucidate outcome effects of epinephrine administration. The primary outcome of 30-day survival was 3.2% in the epinephrine group vs. 2.4% in the saline group (adjusted OR 1.47; 1.09-1.97), with 112 the number needed to treat to prevent one death. Secondary outcomes analyzed were: hospital discharge with favorable neurologic outcomes, 2.2 % in the epinephrine vs. 1.9% in the saline (OR 1.19; 0.85-1.68); 3-month survival – 3% vs. 2.2% (OR 1.47; 1.08-2); favorable neurologic outcome at 3 months 2.1% vs 1.6% (OR 1.39; 0.97-2.01). While the overall survival rate in both groups was very low, the 30-day and 3 month survival was statistically significantly greater in the epinephrine group, and there was a significantly higher rate of ROSC -36.3% vs 11.7%, as well as survival to admission - 23.8% vs 8% (OR 3.83; 3.-4.43); however, the difference in the primary outcome was not as large as hoped, with NNT 112. This trial does not negate the role of epinephrine in out-of-hospital cardiac arrest; rather, it highlights other considerations in the resuscitation process, such as the complexity of the underlying pharmacophysiology, the focus on various aspects of the resuscitation interventions and their impact on outcomes beyond simple survival assessment, as well as on the end points of the resuscitation efforts.

Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599,912 current drinkers in 83 prospective studies.

Wood AM, Kaptoge S, Butterworth AS et al; Emerging Risk Factors Collaboration/EPIC-CVD/UK Biobank Alcohol Study Group.
Lancet. 2018;391:1513-1523.

This study by the an international consortium of data on 786 787 participants found a curvilinear positive correlation between alcohol consumption and all cause-mortality, with the lowest incidence below 100 gm/week. A positive linear associations of alcohol consumption with stroke (HR per 100 g/week higher consumption 1.14; 1.10–1.17), coronary disease excluding myocardial infarction (1.06; 1.00–1.11), heart failure (1.09; 1.03–1.5), fatal hypertensive disease (1.24; 1.15–1.33), and fatal aortic aneurysm (1.15; 1.03–1.28). There was an inverse and approximately log-linear association of alcohol consumption with myocardial infarction (0.94; 0.91–0.97) after adjustment for other major risk factors. Alcohol consumption levels also had a inverse correlation with life expectancy, with the highest divergence in the 4th decade: at age 40, compared to the reported drinkers of 0–≤100 g (mean usual 56 g) alcohol per week, those who reported drinking >100–≤200 g (mean usual 123 g) per week, >200–≤350 g (mean usual 208 g) per week or >350 g (mean usual 367 g) per week had shorter life expectancy respectively of approximately 6 months, 1–2 years, or 4–5 years. The results suggest that for all-cause mortality and morbidity from some cardiovascular disorders, the threshold for the lowest risk is 100 gm per week, while for others there is no low threshold below which the risk association is eliminated, and for myocardial infarction, low level of alcohol has inverse risk correlation.

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