The effect of increasing doses of norepinephrine on tissue oxygenation and microvascular flow in patients with septic shock.

OBJECTIVE: To investigate the effect of escalating doses of norepinephrine, aimed at achieving incremental increases in mean arterial pressure (MAP), on microvascular flow and tissue oxygenation in patients with septic shock. DESIGN: Single-center interventional study. SETTING: University hospital intensive care unit. PATIENTS: Sixteen patients with established septic shock. INTERVENTIONS: The norepinephrine dose was escalated to achieve incremental increases in the MAP from 60 to 70, 80, and 90 mm Hg. MEASUREMENTS AND MAIN RESULTS: In addition to routine clinical measurements, cardiac output was determined using lithium dilution and arterial waveform analysis, cutaneous tissue Pto2 was measured using a Clark electrode, cutaneous red blood cell flux was assessed using laser Doppler flowmetry, and sublingual microvascular flow was evaluated using sidestream darkfield imaging. The mean (sd) norepinephrine dose increased from 0.18 (0.18) microg x kg(-1) x min(-1) at 60 mm Hg to 0.41 (0.26) microg x kg(-1) x min(-1) at 90 mm Hg (p < 0.0001). During this period, global oxygen delivery increased from 487 (418-642) to 662 (498-829) mL x min(-1) x m(-2) (p < 0.01), cutaneous Pto2 increased from 44 (11) to 54 (13) mm Hg (p < 0.0001) and cutaneous microvascular red blood cell flux increased from 26.1 (16.2-41.9) to 33.3 (20.3-46.7) perfusion units (p < 0.05). No changes in sublingual microvascular flow index, vessel density, the proportion of perfused vessels, perfused vessel density, or heterogeneity index were identified by sidestream darkfield imaging. CONCLUSIONS: In patients with septic shock, targeting higher MAP by increasing the dose of norepinephrine resulted in an increase in global oxygen delivery, cutaneous microvascular flow, and tissue oxygenation. There were no changes in preexisting abnormalities of sublingual microvascular flow. Further research is required to clarify the optimal end points for vasopressor therapy in patients with septic shock.

The effect of veno-venous ECMO on the pharmacokinetics of Ritonavir, Darunavir, Tenofovir and Lamivudine.

INTRODUCTION: To our knowledge, there is no published data on the pharmacokinetic (PK) profile of antiretroviral (ART) drugs on patients undergoing extracorporeal membrane oxygenation (ECMO) therapy. We present PK analyses of Ritonavir, Darunavir, Lamivudine and Tenofovir in a patient with HIV who required veno-venous ECMO (VV ECMO). METHODS: Plasma concentrations for Ritonavir, Darunavir, Tenofovir and Lamivudine were obtained while the patient was on ECMO following pre-emptive dose adjustments. Published population PK models were used to simulate plasma concentration profiles for the drugs. The population prediction and the observed plasma concentrations were then overlaid with the expected drug profiles using the individual Bayesian post-hoc parameter estimates. RESULTS: Following dose adjustments, the PK profiles of Ritonavir, Darunavir and Tenofovir fell within the expected range and appeared similar to the population prediction, although slightly different for Ritonavir. The observed data for Lamivudine and its PK profile were completely different from the data available in the literature. CONCLUSIONS: To our knowledge, this is the first study reporting the PK profile of ART drugs during ECMO therapy. Based on our results, dose adjustment of ART drugs while on VV ECMO may be advisable. Further study of the PK profile of Lamivudine is required.

Oxygenation via a Biventricular Assist Device for Emergency Airway Management.

A 56-year-old man receiving mechanical circulatory support via a biventricular assist device suffered an airway emergency secondary to bleeding into the airway. An improvised solution to gain control of the airway in the short term was devised, and an oxygenator was inserted into the circuit, providing an alternative means of gas exchange while definitive control of the airway was achieved. This case changed practice in our institution, where we now make contingency plans for emergency oxygenator insertion into the circuits of all patients with a biventricular assist device who show any sign of airway hemorrhage.

Chronic mould exposure as a risk factor for severe community acquired pneumonia in a patient requiring extra corporeal membrane oxygenation.

A previously fit and well man developed acute respiratory failure due to environmental mould exposure from living in damp rental accommodation. Despite aggressive intensive care management he rapidly deteriorated and required respiratory and cardiac Extracorporeal Membrane Oxygenation. We hypothesize that poor domiciliary conditions may make an underestimated contribution to community respiratory disease. These conditions may present as acute and severe illness with non-typical pathogens identified.