Christophe Vinsonneau

Successful Cardiopulmonary Resuscitation After Cardiac Arrest as a “Sepsis-Like” Syndrome

Background—We investigated the immunoinflammatory profile of patients successfully resuscitated after cardiac arrest, representing a model of whole-body ischemia/reperfusion syndrome. Methods and Results—Plasma cytokine, endotoxin, and ex vivo cytokine production in whole-blood assays was assessed in 61, 35, and 11 patients, respectively. On admission, high levels of plasma interleukin (IL)-6, IL-8, IL-10, and soluble tumor necrosis factor (TNF) receptor type II could discriminate between survivors and nonsurvivors. Among nonsurvivors, the initial need for a vasopressor agent was associated with higher levels of IL-1 receptor antagonist, IL-10, and IL-6 on day 1. Plasma endotoxin was detected in 46% of the analyzed patients within the 2 first days. Endotoxin-induced TNF and IL-6 productions were dramatically impaired in these patients compared with healthy control subjects, whereas an unaltered production was observed with heat-killed Staphylococcus aureus. In contrast, IL-1 receptor antagonist productions were enhanced in these patients compared with healthy control subjects. The productions of T-cell–derived IL-10 and interferon-&ggr; were also impaired in these patients. Finally, using in vitro plasma exchange between healthy control subjects and patients, we demonstrated that the endotoxin-dependent hyporeactivity was an intrinsic property of patients’ leukocytes and that an immunosuppressive activity was also present in their plasma. Conclusions—Altogether, the high levels of circulating cytokines, the presence of endotoxin in plasma, and the dysregulated production of cytokines found in these patients recall the immunological profile found in patients with sepsis.

Hepatic response to sepsis: interaction between coagulation and inflammatory processes.

Objectivesa) To review the hepatic response to sepsis and to establish how this response contributes to coagulation and inflammatory processes; b) to review the physiologic and biochemical mechanisms that suggest hepatic dysfunction may occur during sepsis, enhance procoagulant and proinflammatory activities, and participate in the potential evolution to multiple organ dysfunction syndrome. Data SourcesA summary of published medical literature from MEDLINE search files and published reviews on liver function in experimental and human sepsis. Data SummaryIn sepsis, the liver plays a major role in host defense mechanisms. Kupffer cells are responsible for bacterial scavenging, bacterial products inactivation, and inflammatory mediators clearance and production. Hepatocytes, via receptors for many proinflammatory cytokines, modify their metabolic pathway toward gluconeogenesis, amino-acid uptake, and increased synthesis of coagulant and complement factors and protease inhibitors. The acute-phase protein (APP) response also contributes to the procoagulant state, especially by enhancing the inhibition of protein C (&agr;1-antitrypsin and &agr;2-macroglobulin) and by decreasing liver synthesis of protein C and antithrombin (negative APPs). Elevated C-reactive protein levels (positive APPs) promote the expression of tissue factor by mononuclear cells. Increased liver production of thrombin-activatable fibrinolytic inhibitor (positive APPs) enhances fibrinolysis inhibition. Conversely, such hepatic inflammatory and coagulation processes in sepsis may alter the function of this organ. Indeed, the liver can be injured by activated Kupffer cells that release chemokines, attract blood neutrophils into the liver, and activate them. Neutrophils up-regulate their surface adhesion molecules, tissue factor, and Kupffer cells, whereas tissue factor pathway inhibitor and thrombomodulin are almost undetectable in endothelial cells. This may lead to microcirculatory disturbances, fibrin deposition, hepatocyte injury, endotoxin and bacteria spillover, and multiple organ failure. ConclusionsIn sepsis, the liver participates in host defense and tissue repair through hepatic cell cross-talk that controls most of the coagulation and inflammatory processes. When this control is not adequate, a secondary hepatic dysfunction may occur and may sometimes lead to bacterial products spillover, enhanced procoagulant and inflammatory processes, and in turn, multiple organ failure and death.

Compliance with triage to intensive care recommendations.

Design Recommendations for triage to intensive care units (ICUs) have been issued but not evaluated. Setting In this prospective, multicenter study, all patients granted or refused admission to 26 ICUs affiliated with the French Society for Critical Care were included during a 1-month period. Characteristics of participating ICUs and patients, circumstances of triage, and description of the triage decision with particular attention to compliance with published recommendations were recorded. Results During the study period, 1,009 patients were and 283 were not admitted to the participating ICUs. Refused patients were more likely to be older than 65 yrs (odds ratio [OR], 3.53; confidence interval [CI], 1.98–5.32) and to have a poor chronic health status (OR, 3.09; CI, 2.05–4.67). An admission diagnosis of acute respiratory or renal failure, shock, or coma was associated with admission, whereas chronic severe respiratory and heart failure or metastatic disease without hope of remission were associated with refusal (OR, 2.24; CI, 1.38–3.64). Only four (range, 0–8) of the 20 recommendations for triage to ICU were observed; a full unit and triage over the phone were associated with significantly poorer compliance with recommendations (0 [0–2] vs. 6 [2–9], p = .0003; and 1 [0–6] vs. 6 [1–9], p < .0001; respectively). Conclusion Recommendations for triage to intensive care are rarely observed, particularly when the unit is full or triage is done over the phone. These recommendations may need to be redesigned to improve their practicability under real-life conditions, with special attention to phone triage and triaging to a full unit.

French intensivists do not apply American recommendations regarding decisions to forgo life-sustaining therapy.

ObjectiveRecommendations for making and implementing decisions to forgo life-sustaining therapy in intensive care units have been developed in the United States, but the extent that they are realized in practice has yet to be measured. DesignProspective, multicenter, 4-wk study. For each patient with an implemented decision to forgo life-sustaining therapy, the deliberation and decision implementation procedures were recorded. SettingFrench intensive care units. PatientsAll consecutive patients admitted to 26 French intensive care units. InterventionsNone. Measurements and Main Results Of 1,009 patients admitted, 208 died in the intensive care unit. A decision to forgo life-sustaining therapy was implemented in 105 patients. The number of supportive treatments forgone was 2.3 ± 1.7 per patient. Decisions to forgo sustaining therapy were preceded by 3.5 ± 2.5 deliberation sessions. Proxies were informed of the deliberations in 62 (59.1%) cases but participated in only 18 (17.1%) decisions. The patient’s perception of his or her quality of life was rarely evaluated (11.5%), and only rarely did the decision involve evaluating the patient’s wishes (7.6%), the patient’s religious values (7.6%), or the cost of treatment (7.6%). Factors most frequently evaluated were medical team advice (95.3%), predicted reversibility of acute disease (90.5%), underlying disease severity (83.9%), and the patient’s quality of life as evaluated by caregivers (80.1%). ConclusionsA decision to withhold or withdraw life-sustaining therapy was implemented for half the patients who died in the French intensive care units studied. In many cases, the decision was taken without regard for one or more factors identified as relevant in U.S. guidelines.

Influence of burns on pharmacokinetics and pharmacodynamics of drugs used in the care of burn patients.

The pharmacokinetics and pharmacodynamics of drugs are significantly altered in the burn patient, and the burn patient population shows wide inter- and intraindividual variation in drug handling. Burn injury evolves in two phases. The first phase corresponds to the burn shock, which occurs during the first 48 hours after thermal injury. In this phase, hypovolaemia, oedema, hypoalbuminaemia and a low glomerular filtration rate are observed, which result in a slower rate of drug distribution and lower renal clearance. The second phase (beyond 48 hours after injury) is a hyperdynamic state with high blood flow in the kidneys and liver, an increased α1-acid-glycoprotein level and loss of the drug with exudate leakage. As a result, protein binding, drug distribution and clearance may be altered.Because of the alteration in these variables, wide intraindividual variation of pharmacokinetic parameters occurs depending upon the time since thermal injury and fluid resuscitation. Interindividual variations may be correlated with the percentage of the body surface area that is burnt, creatinine clearance, albuminaemia or the α1-acid-glycoprotein level. A number of important variations in pharmacodynamic parameters have been described, but their mechanisms are poorly understood.From a practical point of view, for the subpopulation of burn patients who eliminate drugs extremely rapidly, higher doses and/or shorter dosing intervals are required to avoid treatment inefficacy. Drug concentration measurements help to take into account interindividual variability. However, adaptation of doses based on Bayesian methods is frequently not possible because the distribution of pharmacokinetic parameters is poorly characterized in this population. Methods based only on individual data or on a surrogate marker for efficacy may be used to optimize the dosing regimen in this population.

Feasibility of Azithromycin Prophylaxis During a Pertussis Outbreak Among Healthcare Workers in a University Hospital in Paris

The objective of the present study was to evaluate the feasibility of azithromycin prophylaxis with respect to tolerability and compliance during a pertussis outbreak among healthcare workers in a university hospital ward. Compliance with the prophylaxis regimen was 89%; compliance was 75% from intent-to-treat perspective. The rate of adverse events was 33%. Female sex was associated with reporting of adverse events. Nonstudents and healthcare workers who reported adverse events were less compliant with the prophylaxis regimen.

HEMOFILTRATION AND LEFT VENTRICULAR FUNCTION IN SEPSIS : MECHANISMS AND CLINICAL IMPLICATIONS

Over the last decade, it became clear that left ventricular (LV) dysfunction is typical of animal and human septic shock [1]. Circulating myocardial depressant substances [2] and local release of mediators [3], rather than global myocardial hypoperfusion [4,5], seem responsible for this phenomenon. Indeed, a series of reports [3] by Parrillo et al. in the 1980s were able to conclusively link left ventricular systolic dysfunction in septic patients to the effects of a myocardial depressant substance in the patients own serum. Moreover, immunoabsorption of both tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta from the sera of patients with septic shock completely eliminated its cardiac myocyte depressant activity, suggesting that TNF-alpha and IL-1 beta contribute to septic myocardial depression [2]. Removing various proinflammatory substances by hemofiltration became consequently very attractive, especially as several studies showed that the left ventricular systolic function of septic animals was improved by hemofiltration and confirmed the presence of a depressive substance in the plasma and ultrafiltrate of septic animals [6,7].

Too early initiation of renal replacement therapy may be harmful

In an observational multicenter study, Elseviers and colleagues report that renal replacement therapy (RRT) in acutely ill patients treated for acute kidney injury is an independent risk factor for death. This result may question the benefit of the current practice of early RRT initiation.

Timing of Initiation of Renal Replacement Therapy in Critically Ill Patients With Acute Kidney Injury

Timing of Initiation of Renal Replacement Therapy in Critically Ill Patients With Acute Kidney Injury To the Editor The Early vs Late Initiation of Renal Replacement Therapy on Mortality in Critically Ill Patients With Acute Kidney Injury (ELAIN) trial reported decreased mortality with early vs delayed renal replacement therapy (RRT) initiation in critically ill patients with acute kidney injury (AKI).1 In contrast, the Artificial Kidney Initiation in Kidney Injury (AKIKI) trial found no mortality difference with early vs delayed strategies.2 However, the design of the 2 studies was different. In the AKIKI trial, late initiation was based on typical absolute criteria (hyperkalemia, metabolic acidosis, pulmonary edema, severe oliguria) compared with a timeframe initiation (<12 hours of reaching Kidney Disease: Improving Global Outcomes [KDIGO] stage 3 AKI) in the ELAIN trial. The case-mix in the 2 studies was different. In the ELAIN study, the population was mostly postoperative patients with approximately 50% having had cardiac surgery, whereas in the AKIKI study, the population was mainly medical (around 80% had sepsis). However, the difference in mortality at 60 days after randomization between the early and delayed strategies was not statistically significant in either study. The effect on mortality in the ELAIN study did not reach significance until day 90. The results of the ELAIN trial raise some concerns. The mortality in the 2 groups appears low given the severity scores (Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment [SOFA]), which predict a mortality as high as 70%. In addition, the difference in mortality at day 90 seems large (54.7% in the delayed group vs 39.3% in the early group; mean reduction, −15.4% [95% CI, −28.1% to −2.6%]). To date, no intervention in the intensive care unit has shown such a positive effect, and it appears improbable that early vs late RRT could achieve this benefit. Even more surprising is the very late effect on mortality. The difference did not become statistically significant until day 90, and the 2 survival curves separated only after the first 10 days. Other factors may explain the results. Editor’s Note: This letter was inadvertently omitted from the September 20 issue.

Efficiency of goal-directed oxygen delivery in ICU patients

BACKGROUND Current clinical practice guidelines promote a goal-directed approach for oxygen delivery with respect to SpO₂ objectives. We evaluated the efficiency of a strategy based on goal-directed O₂ delivery in the ICU. METHODS A group of 30 patients (Group 1) with a proven history of chronic obstructive pulmonary disease suffering from acute hypercarbic exacerbation was compared to 2 other groups of patients admitted for acute respiratory failure with no history of pulmonary disease: 30 patients requiring oxygen supply and/or non-invasive ventilation (Group 2) and 30 requiring invasive ventilation (Group 3). The delivery of oxygen was based on SpO₂ measurement: 88-94% for Group 1 and 90-96% for others. The time spent with an SpO₂ below, within and above the prescribed limits was collected. RESULTS The mean time spent within the prescribed range was for Groups 1, 2 and 3, respectively as follows: 61.9% [60.5-63.2], 63.7% [62.3-65] and 56.4% [55.3-57.6] (P < 0.001 for each group). A history of chronic obstructive pulmonary disease was not correlated with better results (P = 0.11), while invasive ventilation was related to the time spent out of the prescribed range (P < 0.001; OR 1.3 [1.22-1.28]) especially in hyperoxaemia (40.7% [39.6-41.8] P < 0.001). Efficiency seems unrelated to nursing workload or night team exhaustion (r = -0.09, P = 0.77). CONCLUSIONS Goal-directed oxygen delivery based on SpO₂ objectives in ICU patients ensures that in only approximately 64% of the time, SpO₂ stays within the prescribed range.