Principles of environmentally-sustainable anaesthesia: a global consensus statement from the World Federation of Societies of Anaesthesiologists.

The Earth's mean surface temperature is already approximately 1.1°C higher than pre-industrial levels. Exceeding a mean 1.5°C rise by 2050 will make global adaptation to the consequences of climate change less possible. To protect public health, anaesthesia providers need to reduce the contribution their practice makes to global warming. We convened a Working Group of 45 anaesthesia providers with a recognised interest in sustainability, and used a three-stage modified Delphi consensus process to agree on principles of environmentally sustainable anaesthesia that are achievable worldwide. The Working Group agreed on the following three important underlying statements: patient safety should not be compromised by sustainable anaesthetic practices; high-, middle- and low-income countries should support each other appropriately in delivering sustainable healthcare (including anaesthesia); and healthcare systems should be mandated to reduce their contribution to global warming. We set out seven fundamental principles to guide anaesthesia providers in the move to environmentally sustainable practice, including: choice of medications and equipment; minimising waste and overuse of resources; and addressing environmental sustainability in anaesthetists' education, research, quality improvement and local healthcare leadership activities. These changes are achievable with minimal material resource and financial investment, and should undergo re-evaluation and updates as better evidence is published. This paper discusses each principle individually, and directs readers towards further important references.

Eco-responsibility in the operating theater: An urgent need for organizational transformation.

Factors associating environmental degradation with human health have shown that air pollution is a source of morbi-mortality throughout the world. Unfortunately, hospitals are themselves "silent polluters". As healthcare professionals, we are the guarantors not only of quality of patient care, but also of proper hospital conduct. The aim of this attempt at clarification is to outline what can be done in the operating theater to reduce the environmental impact of the treatments we administer. Our recommendations will go above and beyond regulatory frameworks and draw upon daily practice concerning waste management, energy consumption, utilization of anesthetic agents and multiple forms of waste. A number of French and international pilot experimentations have been carried out and could strongly contribute to the modification of clinical practices with a societal impact, at a time when ecology has become one of the main preoccupations of our fellow citizens.

Isolated pelvic perfusion in irradiated unresectable recurrence of pelvic tumor: preliminary outcome and ongoing study.

The technique of isolated pelvic perfusion (IPP) using extracorporeal circulation is capable of delivering high dose chemotherapy in the pelvic cavity. This technique has improved over time, notably with the use of a G-suit placed and inflated above the iliac bifurcation to impede flow through percutaneous vascular routes. This approach is of potential value in patients with previously irradiated, locally advanced recurrences of cancer originating from the gynecological or gastrointestinal organs. Administration of tumor necrosis factor alpha (TNF-α) in combination with melphalan seems to provide response rates similar to those obtained in the technique of isolated extremity perfusion. A preliminary phase I study has shown promising results in terms of feasibility and response rates. A randomized study is currently underway to compare IPP to standard treatment in patients with unresectable recurrent pelvic tumors of gynecological or gastrointestinal origin.

p53 status correlates with histopathological response in patients with soft tissue sarcomas treated using isolated limb perfusion with TNF-alpha and melphalan.

BACKGROUND: Recombinant tumor necrosis factor-alpha (TNF-alpha) combined to melphalan is clinically administered through isolated limb perfusion (ILP) for regionally advanced soft tissue sarcomas of the limbs. In preclinical studies, wild-type p53 gene is involved in the regulation of cytotoxic action of TNF-alpha and loss of p53 function contributes to the resistance of tumour cells to TNF-alpha. The relationship between p53 status and response to TNF-alpha and melphalan in patients undergoing ILP is unknown. PATIENTS AND METHODS: We studied 110 cases of unresectable limbs sarcomas treated by ILP. Immunohistochemistry was carried out using DO7mAb, which reacts with an antigenic determinant from the N-terminal region of both the wild-type and mutant forms of the p53 protein, and PAb1620mAb, which reacts with the 1620 epitope characteristic of the wild-type native conformation of the p53 protein. The immunohistochemistry data were then correlated with various clinical parameters. RESULTS: P53DO7 was found expressed at high levels in 28 patients, whereas PAb1620 was negative in 20. The tumours with poor histological response to ILP with TNF-alpha and melphalan showed significantly higher levels of p53-mutated protein. CONCLUSIONS: Our results might be a clue to a role of p53 protein status in TNF-alpha and melphalan response in clinical use.

Interleukin-1 receptor antagonist production during infectious and noninfectious systemic inflammatory response syndrome.

OBJECTIVE: To analyze the levels of circulating and cell-associated forms of interleukin-1 receptor antagonist (IL-1ra) and the spontaneous and the lipopolysaccharide- or streptococcus-induced ex vivo production of IL-1ra by isolated neutrophils. DESIGN: Cohort study. SETTING: A collaborative study between an intensive care unit and a research laboratory. PATIENTS: Septic patients (those with infectious systemic inflammatory response syndrome [SIRS]) and patients undergoing cardiac surgery with cardiopulmonary bypass (noninfectious SIRS). MEASUREMENTS AND MAIN RESULTS: Both noninfectious and infectious SIRS patients had enhanced levels of plasma IL-1ra. In septic patients, the increased level of IL-1ra associated with circulating leukocytes reflected the higher number of circulating neutrophils, because these cells, as well as peripheral blood mononuclear cells, contained similar levels of cell-associated forms of IL-1ra than those found at homeostasis in healthy controls. The analysis of the in vitro production of IL-1ra by neutrophils showed a decreased capacity of these cells to release the secreted form of IL-1ra on activation in all patients when compared with that capacity in healthy controls. In contrast, the production of the intracellular forms of IL-1ra was not altered in septic patients, but it was diminished in post-cardiopulmonary bypass patients. CONCLUSIONS: The capacity of releasing IL-1ra by activated neutrophils from infectious or noninfectious SIRS patients was diminished. In contrast, the accumulation of intracellular IL-1ra in septic patients was not modified when compared with that in healthy controls. These ex vivo data illustrate that a different gene regulation of the secreted and intracellular forms of IL-1 ra occurs during a pathologic situation like sepsis.

Ex vivo T-lymphocyte derived cytokine production in SIRS patients is influenced by experimental procedures.

Ex vivo production of interleukin-2 (IL-2), IL-4, IL-5, and IL-10 by peripheral blood mononuclear cells (PBMC) was studied in 13 septic patients with infectious systemic inflammatory response syndrome (SIRS) and 13 patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) (noninfectious SIRS). We have investigated the levels of cytokines after activation by either concanavalin A (ConA), phytohemagglutinin (PHA), or anti-CD3 antibodies. In whole blood assays, ConA-induced IL-10 was significantly reduced in both groups of patients compared with healthy controls. In sepsis patients, IL-2, IL-5, and IL-10 productions by isolated PBMC were diminished on ConA-induced activation but not in response to PHA and anti-CD3; in CPB patients, only anti-CD3-induced IL-10 production was significantly reduced. Our data indicate that subtle modifications of the reactivity of circulating cells occur during infectious and noninfectious SIRS. Production of both Th1 and Th2 cytokines can be down-regulated; however, the nature of the SIRS, of the cell population, and of the activator may influence the observation.

Interleukin 8 production in whole blood assays: Is interleukin 10 responsible for the downregulation observed in sepsis?

Reduced cytokine production in ex vivo cultures has been regularly reported in patients suffering from sepsis syndrome. Using whole blood assays, we have now demonstrated that in sepsis patients, normal production of IL-8 was achieved with the higher concentration of lipopolysaccharide (LPS; 1 microg/ml) and with heat-killed streptococci, whereas the IL-8 production induced by lower LPS concentration (0.1 microg/ml) was significantly reduced as compared to healthy controls. In contrast, in patients undergoing cardiac surgery associated with cardio-pulmonary bypass, a group of patients with inflammation in the absence of infectious insult, none of the studied IL-8 productions were affected. Among the various anti-inflammatory cytokines known to regulate IL-8 production which we tested (i.e. IL-4, IL-10, IL-13, TGF-beta), IL-10 was the most active inhibitory cytokine in whole blood assays performed with blood samples from healthy subjects. However, its activity was not influenced by the amounts of LPS used. In addition, IL-10 also inhibited the heat-killed streptococci-induced IL-8 production and was the only cytokine to inhibit the release of IL-8 when TNF was added to LPS. It is worth noting that IL-13 which also inhibited the heat-killed streptococci-induced IL-8 production, failed to do so when the TNF production was analysed. Together, these data suggest that while circulating IL-10 in septic patients may be responsible for the hyporeactivity of circulating leukocytes, its presence is not sufficient to explain the observed dysregulation which occurs in septic patients.

Nitric oxide and almitrine: the definitive answer for hypoxemia.

Hypoxia-induced by acute lung injury results from abnormal ventilation/perfusion ratio distribution towards shunt or low ventilation/perfusion zones. Pharmacological modification of pulmonary blood flow distribution improving ventilation/perfusion ratio should correct hypoxia. The development of inhaled nitric oxide therapy had confirmed this concept, but with a relatively high proportion of 'non responders'. Then development of other drugs used alone or in association with nitric oxide may reinforce the benefit of nitric oxide. This has been tested with almitrine bismesylate, a lipophilic drug that reinforce hypoxic pulmonary vasoconstriction. Using inhaled nitric oxide in combination with almitrine, several studies in adult respiratory distress syndrome or acute lung injury patients have shown spectacular results in term of PaO2 and pulmonary shunt reduction. Moreover, the proportion of responders to this combination seems largely great than those observed for each drug alone. In conclusion, pulmonary blood flow manipulation improving ventilation/perfusion mismatching is one of the major strategies to correct severe hypoxia.

Inhaled nitric oxide, almitrine infusion, or their coadministration as a treatment of severe hypoxemic focal lung lesions.

BACKGROUND: The partition of pulmonary blood flow between normal and shunting zones is an important determinant of oxygen tension in arterial blood (PaO2). The authors hypothesized that the combination of inhaled nitric oxide (iNO) and almitrine infusion might have additional effects related to their pharmacologic properties to improve PaO2. Such a combination was tested in patients with hypoxia caused by focal lung lesions, distinct from the acute respiratory distress syndrome. METHODS: Fifteen patients with hypoxic focal lung lesions despite optimal therapy were included and successively treated with (1) 5 ppm iNO, (2) low-dose almitrine infusion (5.5 +/- 1.7 microg x kg(-1) min(-1)) during iNO, and (3) almitrine infusion alone (with NO turned off). Then iNO was reintroduced and we studied the effect of the coadministration in reducing the fractional concentration of oxygen in inspired gas (FI(O2)) and positive end-expiratory pressure (PEEP) levels. Changes in blood gases and pulmonary and systemic hemodynamics were measured. RESULTS: Systemic hemodynamic variables remained stable in all protocol conditions. Use of iNO improved arterial oxygenation and decreased intrapulmonary shunt. Almitrine similarly improved PaO2 but increased pulmonary artery pressure and right atrial pressure. Coadministration of iNO and almitrine improved PaO2 compared with each drug alone and with control. All patients responded (that is, they had at least a +30% increase in PaO2) to this coadministration. When the drug combination was continued, FI(O2) and PEEP could be reduced over 8 h. The hospital mortality rate was 33% and unrelated to hypoxia. CONCLUSIONS: In hypoxemic focal lung lesions, iNO or low-dose almitrine markedly improved PaO2 to a similar extent. Furthermore, the coadministration amplified the PaO2 increase at a level that allowed reductions in FI(O2) and PEEP levels.

Reduced ex vivo interleukin-8 production by neutrophils in septic and nonseptic systemic inflammatory response syndrome.

Ex vivo cytokine production by circulating lymphocytes and monocytes is reduced in patients with infectious or noninfectious systemic inflammatory response syndrome. Very few studies have addressed the reactivity of polymorphonuclear cells (PMN). To analyze further the relative contribution of systemic inflammatory response syndrome alone or in combination with infection we studied the interleukin-8 (IL-8) production by PMN isolated from patients who had undergone cardiac surgery with cardiopulmonary bypass (CPB) and patients with sepsis. Cells were activated with either lipopolysaccharide (LPS) or heat-killed streptococci. Compared with healthy controls, the release of IL-8 by PMN in both groups of patients was significantly reduced whether activated by LPS, independently of its concentration and origin, or by heat-killed streptococci. These observations suggest that stressful conditions related to inflammation, independently of infection, rapidly dampened the reactivity of circulating PMN. We investigated whether the observed diminished reactivity of PMN might reflect an endotoxin tolerance phenomenon. Our in vitro experiments with PMN from healthy controls indicated that PMN could not be rendered tolerant stricto sensu. However, our data suggested that LPS-induced mediators such as IL-10 may be responsible for the observed anergy in patients.

Transcutaneous CO2 tension effects of clonidine in paediatric caudal analgesia.

In adults, clonidine when added to bupivacaine, results in no detectable respiratory depressant effect except when carbon dioxide challenge is performed. However, to date no investigations have quantified this in children. Twenty-four children (nine months to seven years) were randomized in a double-blind study into two groups. After induction, a caudal block was performed with 1 ml.kg-1 0.25% bupivacaine. Clonidine 1 microgram.kg-1 was added in the clonidine group, and 1 ml normal saline in the placebo group. Patients were monitored in the recovery room for three h from arrival to discharge with continuous pulse oximetry, respiratory rate, a transcutaneous CO2 tension (tcPCO2) every 15 min, and a four point sedation score every 30 min. Mean tcPCO2 and respiratory rate values were not different between the two groups. Apnoea and desaturation less than 97% were not observed. The sedation score decreased with time in both groups, and the score time interval was significantly higher in the clonidine group (P < 0.05). All the patients left the recovery room with a sedation score of 1, excepting four in the clonidine group with a sedation score of 2. Clonidine 1 microgram.kg-1 with 0.25% bupivacaine mixture in caudal analgesia in children did not induce an increase in tcPCO2 despite prolonged sedation.

[Rhabdomyolysis after prolonged surgical procedure in the lithotomy posture]. / Rhabdomyolyse après intervention prolongée en position de lithotomie.

Case report of an obese patient who suffered a bilateral rhabdomyolysis after major abdominal surgery under general anaesthesia combined with thoracic epidural analgesia. The patient was in the lithotomy position during the ten hours time period of the surgery. As the patient was sedated in the intensive care unit, the diagnosis was made more difficult. Clinical signs consisted of pain, oedema and neurosensitive deficit in both legs. Creatinine kinase plasma concentration was increased. Treatment included fluid infusions and fasciotomy. The sequelae were major and consisted mainly in muscular deficiency of both legs. This complication is favoured by prolonged surgery and muscular compression elicited by non physiological positions.