Julien Pottecher

Microcirculatory alterations in traumatic hemorrhagic shock

Objectives:Microcirculatory dysfunction has been well reported in clinical studies in septic shock. However, no clinical studies have investigated microcirculatory blood flow behavior in hemorrhagic shock. The main objective of this study was to assess the time course of sublingual microcirculation in traumatic hemorrhagic shock during the first 4 days after trauma. DesignProspective observational study. SettingICU. PatientsEighteen traumatic hemorrhagic shock patients. InterventionsThe sublingual microcirculation was estimated at the study inclusion after surgical or angiographic embolization to control bleeding (D1), and then three times at 24-hour intervals (D2, D3, and D4). Measurements and Main Results:Sublingual microcirculation was impaired for 72 hours despite restoration of the macrovascular circulation after control of bleeding in traumatic hemorrhagic shock patients. Furthermore, we found significantly higher decreases in the microvascular flow index and proportion of perfused vessels in high Sequential Organ Failure Assessment score patients at D4 (Sequential Organ Failure Assessment score ≥ 6) compared to low Sequential Organ Failure Assessment score patients at D4 (Sequential Organ Failure Assessment score < 6) without any differences in global hemodynamics between these two groups. Finally, the initial proportion of perfused vessels at D1 appears to be a good predictor of high Sequential Organ Failure Assessment score at D4. Conclusions:Alterations of microcirculation in traumatic hemorrhagic shock patients result from the interplay among hemorrhage-induced tissue hypoperfusion, trauma injuries, inflammatory response, and subsequent resuscitation interventions. Despite restoration of the macrocirculation, the sublingual microcirculation was impaired for at least 72 hours. The initial proportion of perfused vessels appears to be a good predictor of high Sequential Organ Failure Assessment score at D4. Further studies are required to firmly establish the link between microvascular alterations and organ dysfunction in traumatic hemorrhagic shock patients.

Effect of Noninvasive Ventilation on Tracheal Reintubation Among Patients With Hypoxemic Respiratory Failure Following Abdominal Surgery: A Randomized Clinical Trial

IMPORTANCE It has not been established whether noninvasive ventilation (NIV) reduces the need for invasive mechanical ventilation in patients who develop hypoxemic acute respiratory failure after abdominal surgery. OBJECTIVE To evaluate whether noninvasive ventilation improves outcomes among patients developing hypoxemic acute respiratory failure after abdominal surgery. DESIGN, SETTING, AND PARTICIPANTS Multicenter, randomized, parallel-group clinical trial conducted between May 2013 and September 2014 in 20 French intensive care units among 293 patients who had undergone abdominal surgery and developed hypoxemic respiratory failure (partial oxygen pressure <60 mm Hg or oxygen saturation [SpO2] ≤90% when breathing room air or <80 mm Hg when breathing 15 L/min of oxygen, plus either [1] a respiratory rate above 30/min or [2] clinical signs suggestive of intense respiratory muscle work and/or labored breathing) if it occurred within 7 days after surgical procedure. INTERVENTIONS Patients were randomly assigned to receive standard oxygen therapy (up to 15 L/min to maintain SpO2 of 94% or higher) (n = 145) or NIV delivered via facial mask (inspiratory pressure support level, 5-15 cm H2O; positive end-expiratory pressure, 5-10 cm H2O; fraction of inspired oxygen titrated to maintain SpO2 ≥94%) (n = 148). MAIN OUTCOMES AND MEASURES The primary outcome was tracheal reintubation for any cause within 7 days of randomization. Secondary outcomes were gas exchange, invasive ventilation-free days at day 30, health care-associated infections, and 90-day mortality. RESULTS Among the 293 patients (mean age, 63.4 [SD, 13.8] years; n=224 men) included in the intention-to-treat analysis, reintubation occurred in 49 of 148 (33.1%) in the NIV group and in 66 of 145 (45.5%) in the standard oxygen therapy group within+ 7 days after randomization (absolute difference, -12.4%; 95% CI, -23.5% to -1.3%; P = .03). Noninvasive ventilation was associated with significantly more invasive ventilation-free days compared with standard oxygen therapy (25.4 vs 23.2 days; absolute difference, -2.2 days; 95% CI, -0.1 to 4.6 days; P = .04), while fewer patients developed health care-associated infections (43/137 [31.4%] vs 63/128 [49.2%]; absolute difference, -17.8%; 95% CI, -30.2% to -5.4%; P = .003). At 90 days, 22 of 148 patients (14.9%) in the NIV group and 31 of 144 (21.5%) in the standard oxygen therapy group had died (absolute difference, -6.5%; 95% CI, -16.0% to 3.0%; P = .15). There were no significant differences in gas exchange. CONCLUSIONS AND RELEVANCE Among patients with hypoxemic respiratory failure following abdominal surgery, use of NIV compared with standard oxygen therapy reduced the risk of tracheal reintubation within 7 days. These findings support use of NIV in this setting. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01971892.

Mitochondria: Mitochondrial participation in ischemia–reperfusion injury in skeletal muscle

Irrespective of the organ involved, restoration of blood flow to ischemic tissue is vital, although reperfusion per se is deleterious. In the setting of vascular surgery, even subtle skeletal muscle ischemia contributes to remote organ injuries and perioperative and long-term morbidities. Reperfusion-induced injury is thought to participate in up to 40% of muscle damage. Recently, the pathophysiology of lower limb ischemia-reperfusion (IR) has been largely improved, acknowledging a key role for mitochondrial dysfunction mainly characterized by impaired mitochondrial oxidative capacity and premature mitochondrial permeability transition pore opening. Increased oxidative stress triggered by an imbalance between reactive oxygen species (ROS) production and clearance, and facilitated by enhanced inflammation, appears to be both followed and instigated by mitochondrial dysfunction. Mitochondria are both actors and target of IR and therapeutic strategies modulating degree of ROS production could enhance protective signals and allow for mitochondrial protection through a mitohormesis mechanism.

Clinical relevance of pulse pressure variations for predicting fluid responsiveness in mechanically ventilated intensive care unit patients: the grey zone approach

IntroductionPulse pressure variation (PPV) has been shown to predict fluid responsiveness in ventilated intensive care unit (ICU) patients. The present study was aimed at assessing the diagnostic accuracy of PPV for prediction of fluid responsiveness by using the grey zone approach in a large population.MethodsThe study pooled data of 556 patients from nine French ICUs. Hemodynamic (PPV, central venous pressure (CVP) and cardiac output) and ventilator variables were recorded. Responders were defined as patients increasing their stroke volume more than or equal to 15% after fluid challenge. The receiver operating characteristic (ROC) curve and grey zone were defined for PPV. The grey zone was evaluated according to the risk of fluid infusion in hypoxemic patients.ResultsFluid challenge led to increased stroke volume more than or equal to 15% in 267 patients (48%). The areas under the ROC curve of PPV and CVP were 0.73 (95% confidence interval (CI): 0.68 to 0.77) and 0.64 (95% CI 0.59 to 0.70), respectively (P <0.001). A grey zone of 4 to 17% (62% of patients) was found for PPV. A tidal volume more than or equal to 8 ml.kg-1 and a driving pressure (plateau pressure - PEEP) more than 20 cmH2O significantly improved the area under the ROC curve for PPV. When taking into account the risk of fluid infusion, the grey zone for PPV was 2 to 13%.ConclusionsIn ventilated ICU patients, PPV values between 4 and 17%, encountered in 62% patients exhibiting validity prerequisites, did not predict fluid responsiveness.

Disseminated Trichosporon mycotoxinivorans, Aspergillus fumigatus, and Scedosporium apiospermum coinfection after lung and liver transplantation in a cystic fibrosis patient.

ABSTRACT Trichosporon mycotoxinivorans is a novel pathogen recently found in cystic fibrosis patients. We report the first case of a disseminated fatal infection with T. mycotoxinivorans associated with invasive Aspergillus fumigatus and Scedosporium apiospermum infection after lung and liver transplantation in a cystic fibrosis patient.

Renal resistive index better predicts the occurrence of acute kidney injury than cystatin C.

ABSTRACT The objective of this study was to determine the predictive value of the renal resistive index (RI) and cystatin C values in serum (SCys) and urine (UCys) in the development of acute kidney injury (AKI) in critically ill patients with severe sepsis or polytrauma. This was a prospective, double-center, descriptive study. There were 58 patients with severe sepsis (n= 28) or polytrauma (n = 30). Renal resistive index, SCys, and UCys were measured within 12 h following admission (day 1 [D1]) to the intensive care unit. Renal function was assessed using the AKI network classification: On day 3 (D3), 40 patients were at stage 0 or 1, and 18 were at stage 2 or 3. Patients with AKI stage 2 or 3 had significantly higher RI (0.80 vs. 0.66, P < 0.0001), SCys (1.23 vs. 0.68 mg/L, P = 0.0002), and UCys (3.32 vs. 0.09 mg/L, P = 0.0008). They also had higher Simplified Acute Physiology Score II, arterial lactate level, and intensive care unit mortality. In multivariate analysis, an RI of greater than 0.707 on D1 was the only parameter predictive of the development of AKI stage 2 or 3 on D3 (P = 0.0004). In the subgroup of patients with AKI stage 2 or 3 on D1, RI remained the only parameter associated with persistent AKI on D3 (P = 0.016). In multivariate analysis comparing the predictive value of RI, SCys, and UCys, RI was the only parameter predictive of AKI stage 2 or 3 on D3. Renal resistive index seems to be a promising tool to assess the risk of AKI.

Plasma fibrinogen level on admission to the intensive care unit is a powerful predictor of postoperative bleeding after cardiac surgery with cardiopulmonary bypass

INTRODUCTION Evidence regarding the behavior of fibrinogen levels and the relation between fibrinogen levels and postoperative bleeding is limited in cardiac surgery under cardiopulmonary bypass (CPB). To evaluate perioperative fibrinogen levels as a predictor of postoperative bleeding in patients undergoing cardiac surgery with CPB. MATERIALS AND METHODS In this prospective, single-center, observational cohort study of 1956 patients following cardiac surgery with CPB, fibrinogen level was measured perioperatively. Excessive bleeding group was defined as patients with a 24-h chest tube output (CTO) exceeded the 90th percentile of distribution. RESULTS The median 24-h CTO was 728.6±431.1ml. A total of 189 patients (9.7%) were identified as having excessive bleeding. At admission to the intensive care (Day 0), the fibrinogen levels were 2.5±0.8g/l and 2.1±0.8g/l in the control and excessive bleeding groups, respectively (P<0.0001). The fibrinogen level on Day 0 was significantly correlated with the 24-h CTO (rho=-0.237; P<0.0001). Multivariate analysis demonstrated that the fibrinogen level at Day 0 was the best perioperative standard laboratory test to predict excessive bleeding (P=0.0001; odds ratio, 0.5), whereas preoperative fibrinogen level was not a predictor. Using receiver operating characteristics curve analyses, the best Day 0 fibrinogen level cutoff to predict postoperative bleeding was 2.2g/l. CONCLUSIONS In this large prospective study, the fibrinogen level upon admission to the intensive care unit after CPB predicted the risk of postoperative bleeding. Our data add to the concern regarding the fibrinogen level threshold that might require fibrinogen concentrate infusion to reduce postoperative blood loss.

Written information that relatives of adult intensive care unit patients would like to receive--a comparison to published recommendations and opinion of staff members.

Objective: Information booklets have not been assessed by the families of intensive care unit (ICU) patients. This study explored the information that the relatives of adult ICU patients wanted to find in the information booklets. Design: Multicenter survey. Setting: Twenty-three French ICUs. Subjects: One close relative of each of 250 consecutive adult patients. Methods: Relatives were asked about the desirability of finding information on each of the 24 topics identified by ICU physicians and listed in guidelines as deserving inclusion in information booklets. Interventions: None. Measurements and Main Results: The 250 patients (61% men) had a mean age of 60 ± 18 years and a mean Simplified Acute Physiology Score II of 48 ± 19; 57% had chronic comorbidities and 41% were surgical patients. At least 72% of the relatives felt that booklets should discuss nosocomial infections, treatment-limitation decisions, access to medical information on the patient, access to medical records, and the meaning of medical terms. Overall, relatives wanted more information than that anticipated by ICU physicians, suggested in guidelines, or found in booklets. However, for at least one of the 24 topics, 38% of relatives indicated that fear or poor comprehension made them unwilling to receive written information. These relatives were younger and had fewer years of formal education than did the other relatives, and they were more likely to be visiting conscious unrestrained patients. Conclusions: Opinions of relatives should be taken into account when designing ICU information booklets. Relatives want more information than that anticipated by physicians or suggested in guidelines, but the youngest or the less-educated ones may respond less favorably to written information.

The Limits of Succinylcholine for Critically Ill Patients

BACKGROUND:Urgent tracheal intubations are common in intensive care units (ICU), and succinylcholine is one of the first-line neuromuscular blocking drugs used in these situations. Critically ill patients could be at high risk of hyperkalemia after receiving succinylcholine because one or more etiologic factors of nicotinic receptor upregulation can be present, but there are few data on its real risk. Our objectives in this study were to determine the factors associated with arterial potassium increase (&Dgr;K) and to assess the occurrence of acute hyperkalemia ≥6.5 mmol/L after succinylcholine injection for intubation in the ICU. METHODS:In a prospective, observational study, all critically ill patients intubated with succinylcholine in an ICU were screened. Only intubations with arterial blood gases and potassium measurements before and after (Kafter) a succinylcholine injection were studied. RESULTS:During 18 months, 131 critically ill patients were intubated after receiving succinylcholine with arterial potassium before and after intubation (Kafter) for a total of 153 intubations. After multivariate analysis, the only factor associated with &Dgr;K was the length of ICU stay before intubation (&rgr; = 0.561, P < 0.001). The factors associated with Kafter ≥6.5 mmol/L (n = 11) were the length of ICU stay (P < 0.001) and the presence of acute cerebral pathology (P = 0.047). The threshold of 16 days was found highly predictive of acute hyperkalemia ≥6.5 with 37% (95% confidence interval: 19%–58%) of Kafter ≥6.5 after the 16th day compared with only 1% (95% confidence interval: 0%–4%) of Kafter ≥6.5 when succinylcholine was injected during the first 16 days. CONCLUSIONS:This study shows that the risk of &Dgr;K after succinylcholine injection is strongly associated with the length of ICU stay. The risk of acute hyperkalemia ≥6.5 mmol/L is highly significant after 16 days.

Remote and local ischemic postconditioning further impaired skeletal muscle mitochondrial function after ischemia-reperfusion

OBJECTIVE Muscular injuries contribute to perioperative and long-term morbidity after vascular surgery in humans. We determined whether local and remote ischemic postconditioning might similarly decrease muscle mitochondrial dysfunction through reduced oxidative stress. METHODS Eighteen male Black-6 mice were divided in three groups: (1) sham mice had no ischemia (sham), (2) ischemia-reperfusion (IR) mice underwent 2-hour tourniquet-induced ischemia on both hind limbs, followed by 2-hour reperfusion, and (3) postconditioning (PoC) mice underwent four bouts of 30-second reperfusion and 30-second ischemia at the onset of reperfusion on the right limb; thus, the right limb underwent local PoC and left limb underwent remote PoC (rPoC). Maximal oxidative capacity (V(max)) of the gastrocnemius muscle mitochondrial respiratory chain was measured. Oxidative stress was evaluated by dihydroethidium staining. Expressions of genes involved in antioxidant defense (superoxide dismutase [SOD1], SOD2, glutathione peroxidase [GPx]), apoptosis (Bax, BclII), and inflammation (interleukin-6) were determined by quantitative real-time polymerase chain reaction. Muscle inflammation was determined using immunohistochemistry. RESULTS IR reduced V(max) (8.5 ± 2.2 vs 10.2 ± 1.8 μmol O(2)/min/g dry weight; P = .034), and increased dihydroethidium staining (134.8%; P = .039). IR decreased GPx expression (-47.9%; P = .048) and increased the proapoptotic marker Bax (255.5%; P = .020). Local PoC and rPoC further increased these deleterious effects. PoC decreased V(max) to 4.4 ± 1.4 μmol O(2)/min/g dry weight (sham vs PoC, -56.9% [P < .001]; IR vs PoC, -48.2% [P < .001]). rPoC similarly reduced V(max) to 5.1 ± 1.9 μmol O(2)/min/g dry weight (sham vs PoC, -50.0% [P < .001]; IR vs PoC, -40.0% [P = .001]). Dihydroethidium staining was further increased by PoC (207.2%; P = .002) and rPoC (305.4%; P < .001) compared with sham and was associated with macrophage infiltration. Local PoC increased SOD1, SOD2, and the antiapoptotic Bcl-2, and rPoC increased Bax (391.6%; P < .001) and the Bax/BclII ratio (621.7%; P < .001). CONCLUSIONS Local and remote ischemic postconditioning further increased injury by enhancing mitochondrial dysfunction, oxidative stress production, and inflammation. Caution should be applied when considering ischemic postconditioning in vascular surgery.