Publications

Our data suggest that the use of warm blood cardioplegia, rather than cold crystalloid cardioplegia, may reduce the inflammatory response to CPB. This observation warrants future randomized investigation to determine its clinical relevance.

We investigated the role of the hepatosplanchnic region in the hyperlactatemia observed during endotoxic shock. The study included 18 dogs anesthetized with pentobarbital and mechanically ventilated. After baseline measurements, including gut lactate production (GLP), liver lactate uptake (LLU), liver lactate extraction (LLE), and hepatosplanchnic lactate production (HSLP), each dog received 2 mg/kg of E. coli endotoxin. After a second set of measurements, cardiac tamponade was induced in 12 dogs (EDTX + Tamp) by repeated injections of normal saline into the pericardial sac to progressively reduce cardiac output and hepatic blood flow. The six remaining dogs served as septic controls (EDTX). From a net lactate consumer before endotoxin infusion, the gut became a lactate producer after the endotoxin infusion, with GLP increasing from -11.4 +/- 27.0 to 32.9 +/- 38.2 x 10(-3) mEq/min (P < 0.05). LLU increased from 48.1 +/- 26.2 to 86.6 +/- 45.2 x 10(-3) mEq/min (P < 0.05), so that LLE and HSLP did not change. In the EDTX + Tamp group, LLE became negative, and HSLP became positive only when hepatic oxygen delivery reached its critical value during cardiac tamponade. In the EDTX group, LLE remained positive and HSLP negative. In endotoxic shock, GLP is increased, but the liver can metabolize this additional load of lactate, so that the hepatosplanchnic area is not a major source of lactate unless the liver becomes profoundly hypoxic.

Norepinephrine is the first line vasopressor used in patients with septic shock. However, norepinephrine doses above 1 µg/kg/min are associated with mortality rates of over 80%, suggesting a need to implement adjunctive strategies prior to reaching this dosage. The present study therefore sought to review the existing and emergent vasopressor agents for patients with refractory septic shock. This paper summarizes the use of vasoactive drugs that may be considered in the context of refractory shock. The clinical application of present and future therapies and the related outcome are discussed. A review of the available literature indicated that vasopressin may be a good first option in patients with refractory septic shock, but evidence remains somewhat sparse. Although the use of vasopressin in these circumstances is likely preferable to the use of terlipressin, a pro-drug with an extended half-life, the use of selepressin, a pure V1 agonist, should be further assessed in future studies. Angiotensin II is another emerging option that uses a different signaling pathway. However, nitric oxide synthase inhibitors and methylene blue do not appear to be appropriate in the management of patients with refractory septic shock. In conclusion, the use of different adjunctive agents in combination with the use of norepinephrine may be useful in patients with refractory septic shock, but care must be taken to avoid excessive vasoconstriction.

These updated definitions and clinical criteria should replace previous definitions, offer greater consistency for epidemiologic studies and clinical trials, and facilitate earlier recognition and more timely management of patients with sepsis or at risk of developing sepsis.

Severe sepsis is frequently associated with microcirculatory abnormalities despite seemingly adequate hemodynamic resuscitation. As increased serum angiotensin II levels may play a role in this dysfunction, we evaluated the microcirculatory effects of enalaprilat in an experimental model of septic shock. One hour after injection of 1.5 g/kg body weight of feces into the abdominal cavity, 16 adult female anesthetized, mechanically ventilated sheep were randomized to receive 2.5 mg enalaprilat or saline. When fluid-resistant hypotension (mean arterial pressure, <65 mmHg) developed, norepinephrine was given up to a maximal dose of 3 μg·kg(-1)·min(-1). The sublingual microcirculation was evaluated using sidestream dark-field videomicroscopy. A cutoff of 20 μm was used to differentiate small and large vessels. Experiments were pursued until the sheep's spontaneous death or for a maximum of 30 h. There were progressive and significant reductions in the proportion of small perfused vessels and in the microvascular flow index for small vessels (both P < 0.01 for trend) during shock and the first 2 h of norepinephrine infusion in the placebo group, which were prevented by the administration of enalaprilat. There were no differences between treated and placebo groups in global hemodynamic variables, time to shock or median survival time (21.8 [18.6-28.8] vs. 22.9 [21.8-30.0] h; P = 0.45). However, oxygen exchange was worse (PaO2/FiO2 ratio, 224 [128-297] vs. 332 [187-450]; P < 0.05), and creatinine concentrations increased more in the treated group (from 0.51 [0.42-0.75] to 1.19 [0.64-1.50] mg·dL(-1); P = 0.04) than in the control group (from 0.55 [0.45-0.62] to 0.78 [0.46-1.78] mg·dL(-1); P = 0.12), Enalaprilat therefore prevented the worsening of sublingual microcirculatory variables in this fluid-resuscitated, hyperdynamic model of septic shock, without significant effect on arterial pressure, but with a possible deleterious effect on renal and lung function.

Introduction. L’hypothermie thérapeutique (HT) améliore le devenir neurologique des survivants à un arrêt cardiaque (AC), mais on connait encore peu l’influence de ce refroidissement sur l’hémodynamique cérébrale après réanimation. Le but de cette étude était d’évaluer les effets de l’HT sur la microcirculation et le métabolisme cérébraux.Patients et Méthodes. Dix cochons (sus scropha) anesthétisés, monitorisés de façon invasive et ventilés mécaniquement ont été randomisés en deux groupes (n = 5) :normothermie (NT, 39.5±1.0 °C) et hypothermie thérapeutique (HT, 34.0±1.0°C). Après 3 min de fibrillation ventriculaire non traitée, la réanimation cardiopulmonaire (RCP) a été commencée et poursuivie pour 3 min avant défibrillation. L’hypothermie a été induite dès le début de la RCP avec perfusion de 30 mL/kg d’une solution salée froide en 60 min, refroidissement évaporatif trans-nasal (Rhinochill, Benechill Inc, USA) et refroidissement de surface par de la glace. L’hypothermie a été maintenue durant 6 heures, suivie d’un réchauffement lent par couvertures thermiques. Le groupe control a reçu la même quantité de liquides en bolus (à 38°C) pendant la RCP et la température a été maintenue à la valeur de base. Des sondes intraparenchymateuses ont été utilisées pour mesurer toutes les heures la température cérébrale (Licox CC1.SB, Integra, NeuroSciences Ltd. Hamphsire, UK), le débit sanguin global cérébral (laser Doppler MNP100XP, Oxyflow, Oxford Optronix, Oxford, UK) et le rapport lactate/pyruvate (RLP, microdialyse CMA20, CMA, Sweden). Après craniectomie gauche, le reseau microvasculaire du cortex frontal a été étudié par videomicroscopie Sidestream Dark-Field (SDF, Microscan, MicroVision Medical, Pays-Bas) au départ (T0), 1 heure après l’induction de l’hypothermie (T1), à la fin de l’hypothermie (T2) e après réchauffement (T3), et aux temps correspondant dans le groupe témoin. La densité de capillaires perfusés (Cerebral perfused capillary density, FCD), le pourcentage de petits vaisseaux perfusés, PPV) et l’index de flux moyen (mean flow index, MFI) ont été calculés avec les formules usuelles.Résultats. Le temps de retour à la circulation spontanée était similaire dans les deux groupes (7 [6-22] min pour NT et 9 [6-21] min pour HT). La perfusion microvasculaire était significativement diminuée après AC dans les deux groupes, mais mieux préservée dans le groupe HT Le rapport L/P était plus élevé dans le groupe NT pendant toute la durée de l’expérience.Conclusion. La microcirculation cérébrale est altérée après AC récupéré ;l’hypothermie limite ces altérations et préserve le métabolisme cérébral.

RBCs of septic patients are characterized by a more spherical shape, a decreased capacity of sphericity in hypo-osmolar solution, and a reduction in the sialic acid content of the RBC membrane. These modifications in RBC shape and membrane may contribute to the RBC rheologic abnormalities frequently described in sepsis.

The results of this heterogenous population of critically ill patients suggest incoherence in fluid responsiveness between systemic and microvascular hemodynamics; larger cohort prospective studies with adequate a priori sample size calculations are needed to confirm these findings.