Olufunmilayo Ogundele

Effect of acute endotoxemia on analog estimates of mean systemic pressure

Dynamic estimates of mean systemic pressure based on a Guytonian analog model (Pmsa) appear accurate under baseline conditions but may not remain so during septic shock because blood volume distribution and resistances between arterial and venous beds may change. Thus, we examined the effect of acute endotoxemia on the ability of Pmsa, estimated from steady-state cardiac output, right atrial pressure, and mean arterial pressure, to reflect our previously validated instantaneous venous return measure of mean systemic pressure (Pmsi), derived from beat-to-beat measures of right ventricular stroke volume and right atrial pressure during positive pressure ventilation. We studied 6 splenectomized pentobarbital-anesthetized close chested dogs. Right ventricular stroke volume was measured by a pulmonary arterial electromagnetic flow probe. Instantaneous venous return measure of mean systemic pressure and Pmsa were calculated during volume loading and removal (±100-mL bolus increments×5) both before (control) and 30 minutes after endotoxin infusion (endo). Cardiac output increased (2628±905 vs 3560±539 mL/min; P<.05) and mean arterial pressure decreased (107±16 vs 56±12 mm Hg; P<.01) during endo. Changes in Pmsi and Pmsa correlated during both control and endo (r2=0.7) with minimal bias by Bland-Altman analysis (mean difference±95% confidence interval, 0.47±5.04 mm Hg). We conclude that changes in Pmsa accurately tracts Pmsi under both control and endo.

Inhaled Carbon Monoxide Protects against the Development of Shock and Mitochondrial Injury following Hemorrhage and Resuscitation

Aims Currently, there is no effective resuscitative adjunct to fluid and blood products to limit tissue injury for traumatic hemorrhagic shock. The objective of this study was to investigate the role of inhaled carbon monoxide (CO) to limit inflammation and tissue injury, and specifically mitochondrial damage, in experimental models of hemorrhage and resuscitation. Results Inhaled CO (250 ppm for 30 minutes) protected against mortality in severe murine hemorrhagic shock and resuscitation (HS/R) (20% vs. 80%; P<0.01). Additionally, CO limited the development of shock as determined by arterial blood pH (7.25±0.06 vs. 7.05±0.05; P<0.05), lactate levels (7.2±5.1 vs 13.3±6.0; P<0.05), and base deficit (13±3.0 vs 24±3.1; P<0.05). A dose response of CO (25–500 ppm) demonstrated protection against HS/R lung and liver injury as determined by MPO activity and serum ALT, respectively. CO limited HS/R-induced increases in serum tumor necrosis factor-α and interleukin-6 levels as determined by ELISA (P<0.05 for doses of 100–500ppm). Furthermore, inhaled CO limited HS/R induced oxidative stress as determined by hepatic oxidized glutathione:reduced glutathione levels and lipid peroxidation. In porcine HS/R, CO did not influence hemodynamics. However, CO limited HS/R-induced skeletal muscle and platelet mitochondrial injury as determined by respiratory control ratio (muscle) and ATP-linked respiration and mitochondrial reserve capacity (platelets). Conclusion These preclinical studies suggest that inhaled CO can be a protective therapy in HS/R; however, further clinical studies are warranted.

Pushing the envelope to reduce sedation in critically ill patients

Background Standard treatment of critically ill patients undergoing mechanical ventilation is continuous sedation. Daily interruption of sedation has a benefi cial eff ect, and in the general intensive care unit of Odense University Hospital, Denmark, standard practice is a protocol of no sedation. We aimed to establish whether duration of mechanical ventilation could be reduced with a protocol of no sedation versus daily interruption of sedation.

Dynamic and Personalized Risk Forecast in Step-Down Units. Implications for Monitoring Paradigms

Rationale: Cardiorespiratory insufficiency (CRI) is a term applied to the manifestations of loss of normal cardiorespiratory reserve and portends a bad outcome. CRI occurs commonly in hospitalized patients, but its risk escalation patterns are unexplored. Objectives: To describe the dynamic and personal character of CRI risk evolution observed through continuous vital sign monitoring of individual step‐down unit patients. Methods: Using a machine learning model, we estimated risk trends for CRI (defined as exceedance of vital sign stability thresholds) for each of 1,971 admissions (1,880 unique patients) to a 24‐bed adult surgical trauma step‐down unit at an urban teaching hospital in Pittsburgh, Pennsylvania using continuously recorded vital signs from standard bedside monitors. We compared and contrasted risk trends during initial 4‐hour periods after step‐down unit admission, and again during the 4 hours immediately before the CRI event, between cases (ever had a CRI) and control subjects (never had a CRI). We further explored heterogeneity of risk escalation patterns during the 4 hours before CRI among cases, comparing personalized to nonpersonalized risk. Measurements and Main Results: Estimated risk was significantly higher for cases (918) than control subjects (1,053; P ≤ 0.001) during the initial 4‐hour stable periods. Among cases, the aggregated nonpersonalized risk trend increased 2 hours before the CRI, whereas the personalized risk trend became significantly different from control subjects 90 minutes ahead. We further discovered several unique phenotypes of risk escalation patterns among cases for nonpersonalized (14.6% persistently high risk, 18.6% early onset, 66.8% late onset) and personalized risk (7.7% persistently high risk, 8.9% early onset, 83.4% late onset). Conclusions: Insights from this proof‐of‐concept analysis may guide design of dynamic and personalized monitoring systems that predict CRI, taking into account the triage and real‐time monitoring utility of vital signs. These monitoring systems may prove useful in the dynamic allocation of technological and clinical personnel resources in acute care hospitals.

Pulmonary Artery Catheterization

Pulmonary artery catheterization has been available as a clinical tool since 1964 and quickly became the gold standard for hemodynamic monitoring of critically ill patients. The pulmonary artery catheter allows simultaneous monitoring of continuously mixed venous O2 saturation (SvO2), cardiac output (CO), right atrial pressure (Pra), pulmonary arterial pressure (Ppa), right ventricular ejection fraction (RVef), and, by mathematical derivation, right ventricular end-diastolic volume (EDV) and, by intermittent distal balloon occlusion, pulmonary artery occlusion pressure (Ppao). No other cardiovascular monitoring device shares this pluripotential presence. While there is no debate about the measurements a pulmonary artery catheter can offer, there is controversy surrounding the benefits of this device. Nonetheless, it is clearly a useful hemodynamic monitoring tool in selected patients. However, the decision to place this invasive device must be based on the specific information sought.

Preload-Dependent Monitoring

Preload-dependent monitoring is an important component of the resuscitation of critically ill patients. Cardiac preload is the maximum degree of myocardial fiber stretch, and increases in preload lead to a larger stroke volume. Although volume expansion is typically the first-line therapy for unstable patients, many are not preload responsive. Patient with hemodynamic compromise can be optimized through a careful assessment of their volume responsiveness. This is best achieved when clinicians understand the limitations of both static and dynamic parameters when making clinical decisions. Use of clinically reliable parameters that identify patients who will respond to volume expansion can help avoid potential harm to nonresponders.