Inhaled Nitric Oxide Treatment for Aneurysmal SAH Patients With Delayed Cerebral Ischemia.

BACKGROUND: We demonstrated experimentally that inhaled nitric oxide (iNO) dilates hypoperfused arterioles, increases tissue perfusion, and improves neurological outcome following subarachnoid hemorrhage (SAH) in mice. We performed a prospective pilot study to evaluate iNO in patients with delayed cerebral ischemia after SAH. METHODS: SAH patients with delayed cerebral ischemia and hypoperfusion despite conservative treatment were included. iNO was administered at a maximum dose of 40 ppm. The response to iNO was considered positive if: cerebral artery diameter increased by 10% in digital subtraction angiography (DSA), or tissue oxygen partial pressure (PtiO2) increased by > 5 mmHg, or transcranial doppler (TCD) values decreased more than 30 cm/sec, or mean transit time (MTT) decreased below 6.5 secs in CT perfusion (CTP). Patient outcome was assessed at 6 months with the modified Rankin Scale (mRS). RESULTS: Seven patients were enrolled between February 2013 and September 2016. Median duration of iNO administration was 23 h. The primary endpoint was reached in all patients (five out of 17 DSA examinations, 19 out of 29 PtiO2 time points, nine out of 26 TCD examinations, three out of five CTP examinations). No adverse events necessitating the cessation of iNO were observed. At 6 months, three patients presented with a mRS score of 0, one patient each with an mRS score of 2 and 3, and two patients had died. CONCLUSION: Administration of iNO in SAH patients is safe. These results call for a larger prospective evaluation.

Dysphagia in Mechanically Ventilated ICU Patients (DYnAMICS): A Prospective Observational Trial.

OBJECTIVES: Swallowing disorders may be associated with adverse clinical outcomes in patients following invasive mechanical ventilation. We investigated the incidence of dysphagia, its time course, and association with clinically relevant outcomes in extubated critically ill patients. DESIGN: Prospective observational trial with systematic dysphagia screening and follow-up until 90 days or death. SETTINGS: ICU of a tertiary care academic center. PATIENTS: One thousand three-hundred four admissions of mixed adult ICU patients (median age, 66.0 yr [interquartile range, 54.0-74.0]; Acute Physiology and Chronic Health Evaluation-II score, 19.0 [interquartile range, 14.0-24.0]) were screened for postextubation dysphagia. Primary ICU admissions (n = 933) were analyzed and followed up until 90 days or death. Patients from an independent academic center served as confirmatory cohort (n = 220). INTERVENTIONS: Bedside screening for dysphagia was performed within 3 hours after extubation by trained ICU nurses. Positive screening triggered confirmatory specialist bedside swallowing examinations and follow-up until hospital discharge. MEASUREMENTS AND MAIN RESULTS: Dysphagia screening was positive in 12.4% (n = 116/933) after extubation (18.3% of emergency and 4.9% of elective patients) and confirmed by specialists within 24 hours from positive screening in 87.3% (n = 96/110, n = 6 missing data). The dysphagia incidence at ICU discharge was 10.3% (n = 96/933) of which 60.4% (n = 58/96) remained positive until hospital discharge. Days on feeding tube, length of mechanical ventilation and ICU/hospital stay, and hospital mortality were higher in patients with dysphagia (all p < 0.001). The univariate hazard ratio for 90-day mortality for dysphagia was 3.74 (95% CI, 2.01-6.95; p < 0.001). After adjustment for disease severity and length of mechanical ventilation, dysphagia remained an independent predictor for 28-day and 90-day mortality (excess 90-d mortality 9.2%). CONCLUSIONS: Dysphagia after extubation was common in ICU patients, sustained until hospital discharge in the majority of affected patients, and was an independent predictor of death. Dysphagia after mechanical ventilation may be an overlooked problem. Studies on underlying causes and therapeutic interventions seem warranted.

Interference of angiotensin II and enalapril with hepatic blood flow regulation.

Acute reduction of portal vein blood flow (Qpv) increases hepatic arterial perfusion (Qha) [the hepatic arterial buffer response (HABR)]. Angiotensin II (AT-II) reduces Qpv, but its effect on HABR is not known. We explored interactions of AT-II and enalapril with hepatic blood flow regulation. Twenty healthy anesthetized pigs were randomized to receive AT-II (n = 8) from 5 to 61 ng/kg per min, enalapril (n = 8) from 3 to 24 µg/kg per h, or saline (n = 4). HABR was assessed by occluding portal vein and expressed as 1) ratio between changes in Qha and Qpv, 2) hepatic arterial conductance (Cha). AT-II infusion increased mean arterial blood pressure from 74 (66-77) mmHg to 116 (109-130) mmHg (median, IQR; P < 0.0001) and decreased cardiac output, Qpv, and renal artery flow (-24%, -28% and -45%, respectively). The fraction of cardiac output of Qha, carotid, and femoral flows increased. With enalapril, blood pressure decreased, whereas cardiac output was maintained with flow redistribution favoring hepatic and renal arteries. In AT-II group, dQha/dQpv increased from 0.06 (0.03, 0.17) to 0.24 (0.13, 0.31) (P = 0.002), but Cha during acute portal vein occlusion decreased from 4.3 (1.6, 6.6) to 2.9 (1.2, 3.7) ml/mmHg (P = 0.003). Both variables remained unchanged in the enalapril group and in controls. AT-II infusion reduces portal flow in parallel with cardiac output and induces a dose-dependent redistribution of flow, favoring brain, hepatic artery, and peripheral tissues at the expense of renal perfusion. During HABR, AT-II decreases Cha but increases Qha compensation, likely as result of increased hepatic arterial perfusion pressure. Enalapril had no effect on HABR.

Effect of treatment delay on disease severity and need for resuscitation in porcine fecal peritonitis.

OBJECTIVE: Early treatment in sepsis may improve outcome. The aim of this study was to evaluate how the delay in starting resuscitation influences the severity of sepsis and the treatment needed to achieve hemodynamic stability. DESIGN: Prospective, randomized, controlled experimental study. SETTING: Experimental laboratory in a university hospital. SUBJECTS: Thirty-two anesthetized and mechanically ventilated pigs. INTERVENTIONS: Pigs were randomly assigned (n=8 per group) to a nonseptic control group or one of three groups in which fecal peritonitis (peritoneal instillation of 2 g/kg autologous feces) was induced, and a 48-hr period of protocolized resuscitation started 6 (ΔT-6 hrs), 12 (ΔT-12 hrs), or 24 (ΔT-24 hrs) hrs later. The aim of this study was to evaluate the impact of delays in resuscitation on disease severity, need for resuscitation, and the development of sepsis-associated organ and mitochondrial dysfunction. MEASUREMENTS AND MAIN RESULTS: Any delay in starting resuscitation was associated with progressive signs of hypovolemia and increased plasma levels of interleukin-6 and tumor necrosis factor-α prior to resuscitation. Delaying resuscitation increased cumulative net fluid balances (2.1±0.5 mL/kg/hr, 2.8±0.7 mL/kg/hr, and 3.2±1.5 mL/kg/hr, respectively, for groups ΔT-6 hrs, ΔT-12 hrs, and ΔT-24 hrs; p<.01) and norepinephrine requirements during the 48-hr resuscitation protocol (0.02±0.04 µg/kg/min, 0.06±0.09 µg/kg/min, and 0.13±0.15 µg/kg/min; p=.059), decreased maximal brain mitochondrial complex II respiration (p=.048), and tended to increase mortality (p=.08). Muscle tissue adenosine triphosphate decreased in all groups (p<.01), with lowest values at the end in groups ΔT-12 hrs and ΔT-24 hrs. CONCLUSIONS: Increasing the delay between sepsis initiation and resuscitation increases disease severity, need for resuscitation, and sepsis-associated brain mitochondrial dysfunction. Our results support the concept of a critical window of opportunity in sepsis resuscitation.