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IMPORTANCE: International guidelines recommend body temperature control below 37.8 °C in unconscious patients with out-of-hospital cardiac arrest (OHCA); however, a target temperature of 33 °C might lead to better outcomes when the initial rhythm is nonshockable. OBJECTIVE: To assess whether hypothermia at 33 °C increases survival and improves function when compared with controlled normothermia in unconscious adults resuscitated from OHCA with initial nonshockable rhythm. DATA SOURCES: Individual patient data meta-analysis of 2 multicenter, randomized clinical trials (Targeted Normothermia after Out-of-Hospital Cardiac Arrest [TTM2; NCT02908308] and HYPERION [NCT01994772]) with blinded outcome assessors. Unconscious patients with OHCA and an initial nonshockable rhythm were eligible for the final analysis. STUDY SELECTION: The study cohorts had similar inclusion and exclusion criteria. Patients were randomized to hypothermia (target temperature 33 °C) or normothermia (target temperature 36.5 to 37.7 °C), according to different study protocols, for at least 24 hours. Additional analyses of mortality and unfavorable functional outcome were performed according to age, sex, initial rhythm, presence or absence of shock on admission, time to return of spontaneous circulation, lactate levels on admission, and the cardiac arrest hospital prognosis score. DATA EXTRACTION AND SYNTHESIS: Only patients who experienced OHCA and had a nonshockable rhythm with all causes of cardiac arrest were included. Variables from the 2 studies were available from the original data sets and pooled into a unique database and analyzed. Clinical outcomes were harmonized into a single file, which was checked for accuracy of numbers, distributions, and categories. The last day of follow-up from arrest was recorded for each patient. Adjustment for primary outcome and functional outcome was performed using age, gender, time to return of spontaneous circulation, and bystander cardiopulmonary resuscitation. MAIN OUTCOMES AND MEASURES: The primary outcome was mortality at 3 months; secondary outcomes included unfavorable functional outcome at 3 to 6 months, defined as a Cerebral Performance Category score of 3 to 5. RESULTS: A total of 912 patients were included, 490 from the TTM2 trial and 422 from the HYPERION trial. Of those, 442 had been assigned to hypothermia (48.4%; mean age, 65.5 years; 287 males [64.9%]) and 470 to normothermia (51.6%; mean age, 65.6 years; 327 males [69.6%]); 571 patients had a first monitored rhythm of asystole (62.6%) and 503 a presumed noncardiac cause of arrest (55.2%). At 3 months, 354 of 442 patients in the hypothermia group (80.1%) and 386 of 470 patients in the normothermia group (82.1%) had died (relative risk [RR] with hypothermia, 1.04; 95% CI, 0.89-1.20; P = .63). On the last day of follow-up, 386 of 429 in the hypothermia group (90.0%) and 413 of 463 in the normothermia group (89.2%) had an unfavorable functional outcome (RR with hypothermia, 0.99; 95% CI, 0.87-1.15; P = .97). The association of hypothermia with death and functional outcome was consistent across the prespecified subgroups. CONCLUSIONS AND RELEVANCE: In this individual patient data meta-analysis, including unconscious survivors from OHCA with an initial nonshockable rhythm, hypothermia at 33 °C did not significantly improve survival or functional outcome.

The optimal calorie and protein intakes at the acute phase of severe critical illness remain unknown. We hypothesised that early calorie and protein restriction improved outcomes in these patients, compared with standard calorie and protein targets.

This study aimed to investigate renal replacement therapy (RRT) practices in a representative nationwide sample of French intensive care units (ICUs).

Acute respiratory distress syndrome (ARDS) is a major complication of COVID-19 and is associated with high mortality and morbidity. We aimed to assess whether intravenous immunoglobulins (IVIG) could improve outcomes by reducing inflammation-mediated lung injury.

Actualmente se discute si la hiperoxia– es decir, la ventilación con altas concentraciones de O2 inspirado (FIO2) – y la hiperoxemiaresultante – o sea, la existencia de tensiones arteriales de O2 (PaO2) suprafisiológicas – tienen utilidad durante el manejo agudo del choque circulatorio. Este concepto se basa en la evidencia experimental de que la hiperoxemia podría contribuir a compensar el desbalance entre la provisión y los requerimientos de O2. Sin embargo, a pesar de que aún es una práctica común, su uso se ve limitado debido a la posible toxicidad del oxígeno debido a una mayor formación de especies reactivas de oxígeno (ROS), especialmente bajo condiciones de isquemia/reperfusión. Varios estudios han reportado que existe una relación con forma de U entre la PaO2 y la mortalidad/morbilidad en pacientes en la UCI. Es interesante que estos estudios, retrospectivos en su mayor parte, encontraron que la mortalidad más baja coincide con una PaO2 ∼150 mmHg durante las primeras 24 h de estancia en la UCI; es decir, con niveles suprafisiológicos. La mayoría de los análisis retrospectivos de gran escala publicados recientemente estudiaron poblaciones generales en UCI, pero existen diferencias significativas de acuerdo con la patología subyacente estudiada, así como si se trata de pacientes bajo tratamiento médico o quirúrgico. Por tanto, hasta donde lo permiten los datos publicados, nos centramos en la necesidad de ventilación mecánica, y en la distinción entre la ausencia o la presencia de choque circulatorio. No parece haber un objetivo ideal de PaO2, excepto que debe evitarse la exposición prolongada (>24 h) a la hipoxemia (PaO2 < 55–60 mmHg) o a tensiones suprafisiológicas (PaO2 >100 mmHg). Por otra parte, la necesidad de ventilación mecánica, la ausencia o presencia de choque circulatorio y la etiología de la disoxia tisular – es decir, si se debe principalmente a un transporte macro- o microcirculatorio de O2 deficiente o a alteraciones en la utilización celular del O2 – pueden determinar si algún grado de hiperoxia tiene efectos colaterales nocivos.

Non-invasive ventilation has never been compared with high-flow oxygen to determine whether it reduces the risk of severe hypoxaemia during intubation. We aimed to determine if preoxygenation with non-invasive ventilation was more efficient than high-flow oxygen in reducing the risk of severe hypoxaemia during intubation.

Patients with obesity are at higher risk for community-acquired and nosocomial infections. However, no study has specifically evaluated the relationship between obesity and ventilator-associated pneumonia (VAP).

Spontaneous breathing trial (SBT) using a T-piece remains the most frequently performed trial before extubation in ICUs.

Patients with sepsis-induced cardiomyopathy with cardiogenic shock have a high mortality. This study assessed venoarterial extracorporeal membrane oxygenation (VA-ECMO) support for sepsis-induced cardiogenic shock refractory to conventional treatments.

L’administration libérale d’oxygène était initialement considérée comme l’un des piliers de la prise en charge des patients admis en réanimation dans un contexte d’état de choc, dans l’objectif de corriger l’inadéquation entre besoins et apports en oxygène. Depuis, cette approche est largement controversée, de nombreuses études ayant démontré un impact négatif de l’hyperoxie. En effet, la toxicité de l’hyperoxie a été prouvée dans plusieurs situations de réanimation, avec une surmortalité dans les contextes de réanimation post-arrêt cardiaque, d’accident vasculaire cérébral ischémique et de traumatisme crânien sévère. Plus récemment, une augmentation de la mortalité a été mise en évidence chez les patients en état de choc exposés à l’hyperoxie. À ce jour, en dehors d’indications particulières (intoxications au CO, embolies gazeuses, accident de décompression), l’administration d’oxygène avec une stratégie restrictive et non plus libérale (objectif prescrit de ne pas excéder une saturation pulsée en oxygène supérieure à 95 %) semble à privilégier. Cette revue a pour objectif, par une approche physiopathologique, de synthétiser les données disponibles de la littérature concernant l’effet de l’hyperoxie chez le patient de réanimation dans diverses situations, et de faire apprécier au clinicien l’impact potentiel d’une administration non raisonnée d’oxygène.

Whether the route of early feeding affects outcomes of patients with severe critical illnesses is controversial. We hypothesised that outcomes were better with early first-line enteral nutrition than with early first-line parenteral nutrition.

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Clinicians must balance the risks from hypotension with the potential adverse effects of vasopressors. Experts have recommended a mean arterial pressure (MAP) target of at least 65 mmHg, and higher in older patients and in patients with chronic hypertension or atherosclerosis. We conducted a systematic review of randomized-controlled trials comparing higher vslower blood pressure targets for vasopressor therapy administered to hypotensive critically ill patients. We searched MEDLINE®, EMBASE™, and the Cochrane Central Register of Controlled Trials for studies of higher vslower blood pressure targets for vasopressor therapy in critically ill hypotensive adult patients. Two reviewers independently assessed trial eligibility based on titles and abstracts, and they then selected full-text reports. Outcomes, subgroups, and analyses were prespecified. We used GRADE (Grading of Recommendations Assessment, Development and Evaluation) to rate the overall confidence in the estimates of intervention effects. Of 8001 citations, we retrieved 57 full-text articles and ultimately included two randomized-controlled trials (894 patients). Higher blood pressure targets were not associated with lower mortality (relative risk [RR], 1.05; 95% confidence interval [CI], 0.90 to 1.23; P= 0.54), and neither age (P= 0.17) nor chronic hypertension (P= 0.32) modified the overall effect. Nevertheless, higher blood pressure targets were associated with a greater risk of new-onset supraventricular cardiac arrhythmia (RR, 2.08; 95% CI, 1.28 to 3.38; P< 0.01). Current evidence does not support a MAP target > 70 mmHg in hypotensive critically ill adult patients requiring vasopressor therapy. Les cliniciens doivent équilibrer les risques liés à l’hypotension aux complications potentielles des vasopresseurs. Des experts ont recommandé de cibler une tension artérielle moyenne (TAM) d’au moins 65 mmHg, et une TAM plus élevée chez les patients atteints d’hypertension chronique, d’athérosclérose ou plus âgés. Nous avons réalisé une revue systématique des études randomisées contrôlées comparant des cibles de tension artérielle plus élevées à plus basses chez des patients hypotendus en état critique recevant un traitement vasopresseur. Nous avons fait des recherches dans les bases de données Medline, EMBASE et dans le registre central des études contrôlées Cochrane afin d’en extraire les études comparant des cibles de tension artérielle plus élevées ou plus basses chez des patients adultes hypotendus et en état critique recevant un traitement vasopresseur. Deux examinateurs ont évalué de façon indépendante l’éligibilité des études selon leur titre et leur résumé, puis sélectionné les articles intégraux. Les critères d’évaluation, sous-groupes et analyses étaient spécifiés au préalable. Nous avons utilisé le système GRADE (Grading of Recommendations Assessment, Development and Evaluation) afin d’évaluer la confiance globale dans les estimations des effets de l’intervention. Parmi les 8001 citations, nous avons extrait 57 articles intégraux et finalement inclus deux études randomisées contrôlées (894 patients). Les cibles de tension artérielle plus élevées n’étaient pas associées à une mortalité plus basse (risque relatif [RR] 1,05; intervalle de confiance [IC] 95 %, 0,90 à 1,23; P= 0,54), et ni l’âge (P= 0,17) ni l’hypertension chronique (P= 0,32) n’ont modifié l’effet global. Cependant, les cibles de tension artérielle plus élevées étaient associées à un risque plus élevé de nouvelle apparition d’une arythmie cardiaque supraventriculaire (RR, 2,08; IC 95 %, 1,28 à 3,38; P< 0,01). Les données probantes actuelles n’appuient pas une cible de TAM supérieure à 70 mmHg chez les patients adultes hypotendus et gravement malades nécessitant un traitement vasopresseur.

There is insufficient research into the use of mechanical ventilation with increased inspiratory oxygen concentration (FiO2) and fluid resuscitation with hypertonic saline solution in patients with septic shock. We tested whether these interventions are associated with reduced mortality.

The number of organ failures has a strong impact on early mortality of allogeneic stem cell transplantation recipients requiring intensive care. However, acute or refractory graft-versus-host disease does not have a significant impact on hospital mortality. Supplemental digital content is available in the text.

The objective of the study to is to determine the characteristics associated with endotracheal intubation in septic shock patients.

Physicians often prescribe vasopressors to correct pathological vasodilation and improve tissue perfusion in patients with septic shock, but the evidence to inform practice on vasopressor dosing is weak. We undertook a systematic review of clinical studies evaluating different blood pressure targets for the dosing of vasopressors in septic shock. We searched MEDLINE, EMBASE, CENTRAL (to November 2013), reference lists from included articles, and trial registries for randomized controlled trials (RCTs) and observational and crossover intervention studies comparing different blood pressure targets for vasopressor therapy in septic shock. Two reviewers independently selected eligible studies and extracted data on standardized forms. We identified 2 RCTs and 10 crossover trials but no observational studies meeting our criteria. Only one RCT measured clinical outcomes after comparing mean arterial pressure targets of 80 to 85 mmHg versus 65 to 70 mmHg. There was no effect on 28-day mortality, but confidence intervals were wide (hazard ratio, 95 confidence interval 95 CI 0.84 – 1.38). In contrast, this intervention was associated with a greater risk of atrial fibrillation (relative risk, 2.36; 95 CI, 1.18 – 4.72) and a lower risk of renal replacement therapy in hypertensive patients (relative risk, 0.75; 95 CI, 0.57 – 1.0). Crossover trials suggest that achieving higher blood pressure targets by increasing vasopressor doses increases heart rate and cardiac index with no effect on serum lactate. Our findings underscore the paucity of clinical evidence to guide the administration of vasopressors in critically ill patients with septic shock. Further rigorous research is needed to establish an evidence base for vasopressor administration in this population.

When used as a pretreatment, hydrogen sulfide (H2S) either attenuated or aggravated lung injury. Therefore, we tested the hypothesis whether posttreatment intravenous Na2S (sulfide) may attenuate lung injury.

Inhaling hydrogen sulfide (H2S) reduced energy expenditure resulting in hypothermia. Because the inflammatory effects of either hypothermia alone or H2S per se still are a matter of debate, we tested the hypothesis whether inhaled H2S amplifies the hypothermia-related modulation of the inflammatory response. Fifteen hours after cecal ligation and puncture or sham laparotomy, anesthetized and mechanically ventilated normothermic and hypothermic mice (core temperature kept at 38°C and 27°C, respectively) received either 100 ppm H2S or vehicle. In the sham-operated animals, inhaled H2S and hypothermia alone comparably reduced the plasma chemokine and IL-6 levels, but combining hypothermia and inhaled H2S had no additional effect. The lung tissue cytokine and chemokine patterns revealed a similar response. During sepsis, inhaled H2S reduced the blood cytokine concentrations only, without effects on the plasma chemokine or the lung tissue levels. Again, inhaled H2S had no major additional effect during hypothermia. With or without sepsis, inhaled H2S and hypothermia alone comparably reduced the lung tissue heme oxygenase 1 expression, whereas inhaled H2S had no additional effect during hypothermia. Lung tissue nuclear transcription factor B activation was reduced by combining H2S with hypothermia in the sham-operated animals, whereas it was increased by inhaled H2S during sepsis. Hypothermia amplified this response. Hence, during anesthesia and mechanical ventilation, inhaled H2S exerted anti-inflammatory effects, which were, however, not amplified by adding deliberate hypothermia. Sepsis attenuated these anti-inflammatory effects of inhaled H2S, which were at least in part independent of the nuclear transcription factor B pathway.

In sepsis, inflammation and thrombosis are both the cause and the result of interactions between circulating (for example, leukocytes and platelets), endothelial and smooth muscle cells. Microparticles are proinflammatory and procoagulant fragments originating from plasma membrane generated after cellular activation and released in body fluids. In the vessel, they constitute a pool of bioactive effectors pulled from diverse cellular origins and may act as intercellular messengers. Microparticles expose phosphatidylserine, a procoagulant phospholipid made accessible after membrane remodelling, and tissue factor, the initiator of blood coagulation at the endothelial and leukocyte surface. They constitute a secretion pathway for IL-1β and up-regulate the proinflammatory response of target cells. Microparticles circulate at low levels in healthy individuals, but undergo phenotypic and quantitative changes that could play a pathophysiological role in inflammatory diseases. Microparticles may participate in the pathogenesis of sepsis through multiple ways. They are able to regulate vascular tone and are potent vascular proinflammatory and procoagulant mediators. Microparticles' abilities are of increasing interest in deciphering the mechanisms underlying the multiple organ dysfunction of septic shock.

Vasopressin and terlipressin, a long-acting V1a analogue, are increasingly used in intensive care. The main clinical indications are the treatment of patients with septic shock and of patients with cirrhosis, who develop variceal bleeding, the hepatorenal syndrome or both. In this review, we summarize the effects of these drugs on splanchnic hemodynamics and organ function.

Hydrogen sulfide (H2S), a gas with the characteristic odor of rotten eggs, is known for its toxicity and as an environmental hazard, inhibition of mitochondrial respiration resulting from blockade of cytochrome c oxidase being the main toxic mechanism. Recently, however, H2S has been recognized as a signaling molecule of the cardiovascular, inflammatory and nervous systems, and therefore, alongside nitric oxide and carbon monoxide, is referred to as the third endogenous gaseous transmitter. Inhalation of gaseous H2S as well as administration of inhibitors of its endogenous production and compounds that donate H2S have been studied in various models of shock. Based on the concept that multiorgan failure secondary to shock, inflammation and sepsis may represent an adaptive hypometabolic reponse to preserve ATP homoeostasis, particular interest has focused on the induction of a hibernation-like suspended animation with H2S. It must be underscored that currently only a limited number of data are available from clinically relevant large animal models. Moreover, several crucial issues warrant further investigation before the clinical application of this concept. First, the impact of hypothermia for any H2S-related organ protection remains a matter of debate. Second, similar to the friend and foe character of nitric oxide, no definitive conclusions can be made as to whether H2S exerts proinflammatory or anti-inflammatory properties. Finally, in addition to the question of dosing and timing (for example, bolus administration versus continuous intravenous infusion), the preferred route of H2S administration remains to be settled – that is, inhaling gaseous H2S versus intra-venous administration of injectable H2S preparations or H2S donors. To date, therefore, while H2S-induced suspended animation in humans may still be referred to as science fiction, there is ample promising preclinical data that this approach is a fascinating new therapeutic perspective for the management of shock states that merits further investigation.

Human serum albumin (HSA) is used as a resuscitation fluid in sepsis. This study investigated the potential protective properties of HSA on vascular function in a mouse endotoxic model in terms of oxidative and nitrosative stresses. Swiss mice were treated with either lipopolysaccharide (LPS) (50 mg/kg i.p.) or vehicle. One and five hours later, mice were infused with HSA (4%, 10 ml/kg), normal saline (0.9% NaCl, 30 ml/kg), or no fluid. Six hours after treatment, vascular reactivity was assessed on aortae and small mesenteric arteries. Measurements of NO and superoxide anion (O2−) by spin trapping and nuclear factor (NF)-κB, inducible NO synthase (iNOS), and peroxynitrite by Western blotting and immunohistochemical studies were conducted. HSA partially prevented the reduction of blood pressure induced by LPS and completely prevented both vascular hyporeactivity to phenylephrine and myogenic tone as well as endothelial dysfunction induced by the endotoxin. This was associated with a decreased up-regulation of NF-κ B, iNOS, and peroxynitrite in the vascular wall. LPS-induced tissue increases in both NO and O2−production was decreased by HSA. These data demonstrate the protective effect of HSA treatment in experimental endotoxic shock by reducing the inflammatory process leading to oxidative and nitrosative stresses and vascular hyporeactivity.

The organs of the hepatosplanchnic system are considered to play a key role in the development of multiorgan failure during septic shock. Impaired oxygenation of the intestinal mucosa can lead to disruption of the intestinal barrier, which may promote a vicious cycle of inflammatory response, increased oxygen demand and inadequate oxygen supply. Standard septic shock therapy includes supportive treatment such as fluid resuscitation, administration of vasopressors (adrenergic and nonadrenergic drugs), and respiratory and renal support. These therapies may have beneficial or detrimental effects not only on systemic haemodynamics but also on splanchnic haemodynamics, at both the macrocirculatory and microcirculatory levels. This clinical review focuses on the splanchnic haemodynamic and metabolic effects of standard therapies used in patients with septic shock, as well as on the recently described nonconventional therapies such as vasopressin, prostacyclin and N-acetyl cysteine.

Heme oxygenase (HO) has both deleterious and protective effects in various shock models. Most of these data have been derived from experiments with hypodynamic shock states associated with depressed cardiac output. Therefore we studied the role of HO during long-term porcine hyperdynamic endotoxemia characterized by a sustained increase in cardiac output resulting from colloid resuscitation to maintain mean arterial pressure > 60 mmHg. Systemic, pulmonary, and hepatosplanchnic hemodynamic and metabolic effects of the HO-inhibitor tin–mesoporphyrin (SnMP) were assessed in anesthetized and mechanically ventilated animals. After 12 h of continuous intravenous lipopolysaccharide (LPS), animals received either vehicle (n 6) or SnMP (n 8; 6 mol kg−1i.v. over 30 min at 12 and 18 h of LPS). Measurements were performed before LPS, before SnMP infusion, and at 24 h of LPS. SnMP did not influence systemic hemodynamics but significantly increased mean pulmonary artery pressure. Although liver blood flow was not affected, SnMP markedly impaired liver lactate clearance. HO inhibition was associated with increased plasma nitrate levels likely the result of increased NO production. Our results suggest a protective role of HO activation during hyperdynamic porcine endotoxemia possibly as a result of an interaction with the LPS-induced increase in NO formation.

Activation of the poly(ADP-ribose)polymerase (PARP), a highly energy-consuming DNA-repairing enzyme, plays a crucial role in the pathogenesis of multiorgan failure. Most results, however, were derived from experiments with hypodynamic shock states characterized by a markedly decreased cardiac output (CO) and/or using a pretreatment approach. Therefore, we investigated the effects of the novel potent and selective PARP-1 inhibitor PJ34 in a posttreatment model of long-term, volume-resuscitated porcine endotoxemia. Anesthetized, mechanically ventilated and instrumented pigs received continuous intravenous (i.v.) lipopolysaccharide (LPS) over 24 h. Hydroxyethyl starch was administered to maintain a mean arterial pressure > 65 mmHg. After 12 h of LPS infusion, the animals were randomized to receive either vehicle (Control, n 9) or i.v. PJ34 (n 6; 10 mg/kg over 1 h followed by 2 mg/kg/h until the end of the experiment). Measurements were performed before as well as at 12, 18, and 24 h of LPS infusion. In all animals CO increased because of reduced systemic vascular resistance (SVR) and fluid resuscitation. PJ34 further raised CO (P< 0.05 vs. control group) as the result of a higher stroke volume indicating its positive inotropic effect. In addition, it diminished the rise in the ileal mucosal-arterial PCO2gap, which returned to baseline levels at 24 h of LPS, and improved the gut lactate balance (P0.093 PJ34 vs. control) together with significantly lower portal venous lactate/pyruvate ratios. By contrast, it failed to influence the LPS-induced derangements of liver metabolism. Incomplete PARP inhibition because of dilutional effects and/or an only partial efficacy when used in post-treatment approaches may account for this finding.

Targeted temperature management (TTM) currently is the only treatment with demonstrated efficacy in attenuating the harmful effects on the brain of ischemia-reperfusion injury after cardiac arrest. However, whether TTM is beneficial in the subset of patients with in-hospital cardiac arrest (IHCA) remains unclear.

During advanced vasodilatory shock, arginine vasopressin (AVP) is increasingly used to restore blood pressure and thus to reduce catecholamine requirements. The AVP-related rise in mean arterial pressure is due to systemic vasoconstriction, which, depending on the infusion rate, may also reduce coronary blood flow despite an increased coronary perfusion pressure. In a murine model of myocardial ischaemia, Indrambarya and colleagues now report that a 3-day infusion of AVP decreased the left ventricular ejection fraction, ultimately resulting in increased mortality, and thus compared unfavourably with a standard treatment using dobutamine. The AVP-related impairment myocardial dysfunction did not result from the increased left ventricular afterload but from a direct effect on cardiac contractility. Consequently, the authors conclude that the use of AVP should be cautioned in patients with underlying cardiac disease.

In patients with hyperdynamic hemodynamics, infusing arginine vasopressin (AVP) in advanced vasodilatory shock is usually accompanied by a decrease in cardiac output and in visceral organ blood flow. Depending on the infusion rate, this vasoconstriction also reduces coronary blood flow despite an increased coronary perfusion pressure. In a porcine model of transitory myocardial ischemia-induced left ventricular dysfunction, Müller and colleagues now report that the AVP-related coronary vaso-constriction may impede diastolic relaxation while systolic contraction remains unaffected. Although any AVP-induced myocardial ischemia undoubtedly is a crucial safety issue, these findings need to be discussed in the context of the model design, the dosing of AVP as well as the complex direct, afterload-independent and systemic, vasoconstriction-related effects on the heart.

Infusing arginine vasopressin (AVP) in advanced vasodilatory shock is usually accompanied by a decrease in cardiac index and systemic oxygen transport. Whether or not such a vasoconstriction impedes regional blood flow and thus visceral organ function, even when low AVP is used, is still a matter of debate. Krejci and colleagues now report, in this issue of Critical Care, that infusing 'low-dose' AVP during early, short-term, normotensive and normodynamic fecal peritonitis-induced porcine septicemia markedly reduced both renal and portal blood flow, and consequently total hepatic blood flow, whereas hepatic arterial flow was not affected. This macrocirculatory response was concomitant with reduced kidney microcirculatory perfusion, whereas liver micro-circulation remained unchanged. From these findings the authors conclude that the use of AVP to treat hypotension should be cautioned against in patients with septic shock. Undoubtedly, given its powerful vasoconstrictor properties, which are not accompanied by positive inotropic qualities (in contrast with most of the equally potent standard care 'competitors', namely catecholamines), the safety of AVP is still a matter of concern. Nevertheless, the findings reported by Krejci and colleagues need to be discussed in the context of the model design, the timing and dosing of AVP as well as the complex interaction between visceral organ perfusion and function.

No relevant conflicts of interest to declare.

Hydrogen sulfide (H2S) has been shown to improve survival in rodent models of lethal hemorrhage. Conversely, other authors have reported that inhibition of endogenous H2S production improves hemodynamics and reduces organ injury after hemorrhagic shock. Since all of these data originate from unresuscitated models and/or the use of a pre-treatment design, we therefore tested the hypothesis that the H2S donor, sodium hydrosulfide (NaHS), may improve hemodynamics in resuscitated hemorrhagic shock and attenuate oxidative and nitrosative stresses.

Infusing arginine vasopressin (AVP) in vasodilatory shock usually decreases cardiac output and thus systemic oxygen transport. It is still a matter of debate whether this vasoconstriction impedes visceral organ blood flow and thereby causes organ dysfunction and injury. Therefore, we tested the hypothesis whether low-dose AVP is safe with respect to liver, kidney, and heart function and organ injury during resuscitated septic shock.