Spontaneous breathing during extracorporeal membrane oxygenation treatment of sickle cell disease acute chest syndrome.

Sickle cell disease (SCD) is a hereditary hemoglobinopathy resulting in sickling hemoglobin. Acute chest syndrome (ACS) is a serious complication of SCD and an important cause of morbidity and mortality. Management of ACS is complex and may necessitate mechanical ventilation and veno-venous extracorporeal membrane oxygenation (VV-ECMO) therapy in the more severe cases. We present herein the case of a young female adult (19 y.o.) with SCD who developed severe respiratory failure due to ACS occurring twice within 15 months and treated by VV-ECMO. We describe the management of ACS with VV-ECMO using two different approaches, namely with and without mechanical ventilation.

Vasoplegia treatments: the past, the present, and the future.

Vasoplegia is a ubiquitous phenomenon in all advanced shock states, including septic, cardiogenic, hemorrhagic, and anaphylactic shock. Its pathophysiology is complex, involving various mechanisms in vascular smooth muscle cells such as G protein-coupled receptor desensitization (adrenoceptors, vasopressin 1 receptors, angiotensin type 1 receptors), alteration of second messenger pathways, critical illness-related corticosteroid insufficiency, and increased production of nitric oxide. This review, based on a critical appraisal of the literature, discusses the main current treatments and future approaches. Our improved understanding of these mechanisms is progressively changing our therapeutic approach to vasoplegia from a standardized to a personalized multimodal treatment with the prescription of several vasopressors. While norepinephrine is confirmed as first line therapy for the treatment of vasoplegia, the latest Surviving Sepsis Campaign guidelines also consider that the best therapeutic management of vascular hyporesponsiveness to vasopressors could be a combination of multiple vasopressors, including norepinephrine and early prescription of vasopressin. This new approach is seemingly justified by the need to limit adrenoceptor desensitization as well as sympathetic overactivation given its subsequent deleterious impacts on hemodynamics and inflammation. Finally, based on new pathophysiological data, two potential drugs, selepressin and angiotensin II, are currently being evaluated.

Outcome of patients with septic shock and high-dose vasopressor therapy.

BACKGROUND: Despite the dissemination of international guidelines, mortality from septic shock remains high. Norepinephrine is recommended as first-line vasopressor therapy with a target mean arterial pressure of 65 mmHg. High-dose vasopressor (HDV) may also be required. This study aimed to assess survival in patients with septic shock requiring HDV. We conducted a retrospective study of patients admitted between January 2008 and December 2013 to a 13-bed ICU for septic shock and receiving high-dose vasopressor therapy (defined by a dose >1 µg/kg/min). Primary outcome was 28-day mortality (D28). Secondary outcomes were 90-day mortality (D90), organ failure score (SOFA), duration of organ failure, duration and dosage of vasopressor agent and ischemic complications. RESULTS: In our cohort of 106 patients, mortality reached 60.4% at D28 and 66.3% at D90. One in two patients died before D10. The weight-based mean dose of vasopressor (WMD) represented the best prognostic factor. Using a cutoff of 0.75 µg/kg/min, WMD was associated with mortality with a sensitivity of 73% and specificity of 74%. The mortality rate reached 86.4% when WMD was above the cutoff value and associated with a SOFA score >10. Digital or limb necrosis was documented in 6 patients (5.7%). CONCLUSIONS: In total, 40% of septic shock patients receiving high-dose vasopressor therapy survived at day 28 after admission. A WMD cutoff value of 0.75 µg/kg/min, associated with a >10 SOFA score, was a strong predictor of death. These results provide insights into outcome of refractory septic shock, showing that administration of high-dose vasopressor may indeed be useful in these patients.

Beneficial Effects of Norepinephrine Alone on Cardiovascular Function and Tissue Oxygenation in a Pig Model of Cardiogenic Shock.

INTRODUCTION: The present study was developed to investigate the effects of norepinephrine alone on hemodynamics and intrinsic cardiac function in a pig model of cardiogenic shock mimicking the clinical setting. METHODS: Cardiogenic shock was induced by 1-h ligation of the left anterior descending (LAD) artery followed by reperfusion. Pigs were monitored with a Swan-Ganz catheter, a transpulmonary thermodilution catheter, and a conductance catheter placed in the left ventricle for pressure-loop measurements. Measurements were performed before LAD occlusion, 1 h after LAD occlusion, and 4 h after myocardial reperfusion. RESULTS: Myocardial infarction and reperfusion was followed by cardiogenic shock characterized by a significant increase in heart rate and significant decreases in mean arterial pressure (MAP), mixed venous oxygen saturation (SVO2), left ventricular end-diastolic pressure (LVEDP), prerecruitable stroke work (PRSW), and cardiac power index (CPI). Lactate levels were significantly increased. The systemic vascular resistance index (SVRI) and global end-diastolic volume index (GEDVI) remained unchanged. When compared with the control group (n = 6), norepinephrine infusion (n = 6) was associated with no changes in heart rate, a significant increase in MAP, SVO2, left ventricular ejection fraction, pressure development during isovolumic contraction, SVRI, and CPI and a decrease in lactate level. Cardiac index tended to increase (P = 0.059), whereas PRSW did not change in the norepinephrine group. LVEDP and GEDVI remained unchanged. CONCLUSIONS: Norepinephrine alone is able to improve hemodynamics, cardiac function, and tissue oxygenation in a pig model of ischemic cardiogenic shock.

Hemodynamic consequences of severe lactic acidosis in shock states: from bench to bedside.

Lactic acidosis is a very common biological issue for shock patients. Experimental data clearly demonstrate that metabolic acidosis, including lactic acidosis, participates in the reduction of cardiac contractility and in the vascular hyporesponsiveness to vasopressors through various mechanisms. However, the contributions of each mechanism responsible for these deleterious effects have not been fully determined and their respective consequences on organ failure are still poorly defined, particularly in humans. Despite some convincing experimental data, no clinical trial has established the level at which pH becomes deleterious for hemodynamics. Consequently, the essential treatment for lactic acidosis in shock patients is to correct the cause. It is unknown, however, whether symptomatic pH correction is beneficial in shock patients. The latest Surviving Sepsis Campaign guidelines recommend against the use of buffer therapy with pH ≥7.15 and issue no recommendation for pH levels <7.15. Furthermore, based on strong experimental and clinical evidence, sodium bicarbonate infusion alone is not recommended for restoring pH. Indeed, bicarbonate induces carbon dioxide generation and hypocalcemia, both cardiovascular depressant factors. This review addresses the principal hemodynamic consequences of shock-associated lactic acidosis. Despite the lack of formal evidence, this review also highlights the various adapted supportive therapy options that could be putatively added to causal treatment in attempting to reverse the hemodynamic consequences of shock-associated lactic acidosis.