Multicentre, prospective, double-blind, randomised controlled clinical trial comparing different non-opioid analgesic combinations with morphine for postoperative analgesia: the OCTOPUS study.

BACKGROUND: Head-to-head comparisons of combinations of more than one non-opioid analgesic (NOA) with morphine alone, for postoperative analgesia, are lacking. The objective of this multicentre, randomised, double-blind controlled trial was to compare the morphine-sparing effects of different combinations of three NOAs-paracetamol (P), nefopam (N), and ketoprofen (K)-for postoperative analgesia. METHODS: Patients from 10 hospitals were randomised to one of eight groups: control (C) received saline as placebo, P, N, K, PN, PK, NK, and PNK. Treatments were given intravenously four times a day during the first 48 h after surgery, and morphine patient-controlled analgesia was used as rescue analgesia. The outcome measures were morphine consumption, pain scores, and morphine-related side-effects evaluated 24 and 48 h after surgery. RESULTS: Two hundred and thirty-seven patients undergoing a major surgical procedure were included between July 2013 and November 2016. Despite a failure to reach a calculated sample size, 24 h morphine consumption [median (inter-quartile range)] was significantly reduced in the PNK group [5 (1-11) mg] compared with either the C group [27 (11-42) mg; P<0.05] or the N group [21 (12-29) mg; P<0.05]. Results were similar 48 h after surgery. Patients experienced less pain in the PNK group compared with the C, N, and P groups. No difference was observed in the incidence of morphine-related side-effects. CONCLUSIONS: Combining three NOAs with morphine allows a significant morphine sparing for 48 h after surgery associated with superior analgesia the first 24 h when compared with morphine alone. CLINICAL TRIAL REGISTRATION: EudraCT: 2012-004219-30; NCT01882530.

Effect of preoxygenation using non-invasive ventilation before intubation on subsequent organ failures in hypoxaemic patients: a randomised clinical trial.

BACKGROUND: Previous data showed that non-invasive ventilation (NIV) applied for 3 min before tracheal intubation ensured better oxygenation compared with using a non-rebreather bag-valve-mask. We aimed to determine whether preoxygenation using NIV is effective in reducing the incidence of organ dysfunction in hypoxaemic, critically ill patients in intensive care. METHODS: A multicentre, randomised, open-label trial evaluating 100% FiO2 administered with NIV (99 patients) vs with face mask (102 patients) for 3 min before tracheal intubation. The primary endpoint was the maximal value of Sequential Organ Failure Assessment score within 7 days after intubation. RESULTS: The median (inter-quartile range) values of the maximal value of the Sequential Organ Failure Assessment score within 7 days post-intubation were not significantly different between the two randomised groups: nine (6-12) in the NIV group vs 10 (6-12) in the face mask group (P=0.65). In patients treated by NIV prior to the randomisation, there was a significant increase in the occurrence in adverse events in patients randomised to face mask [odds ratio=5.23 (1.61;16.99), P=0.0059]. CONCLUSIONS: This study failed to demonstrate any benefits of using NIV as a preoxygenation method to reduce organ dysfunction compared with usual preoxygenation in hypoxaemic, critically ill patients requiring tracheal intubation for invasive ventilation. NIV should not be discontinued for preoxygenation in the cases of patients treated by NIV before the decision to intubate. CLINICAL TRIAL REGISTRATION: NCT00472160.

A systematic review and consensus definitions for standardised end-points in perioperative medicine: pulmonary complications.

BACKGROUND: There is a need for robust, clearly defined, patient-relevant outcome measures for use in randomised trials in perioperative medicine. Our objective was to establish standard outcome measures for postoperative pulmonary complications research. METHODS: A systematic literature search was conducted using MEDLINE, Web of Science, SciELO, and the Korean Journal Database. Definitions were extracted from included manuscripts. We then conducted a three-stage Delphi consensus process to select the optimal outcome measures in terms of methodological quality and overall suitability for perioperative trials. RESULTS: From 2358 records, the full texts of 81 manuscripts were retrieved, of which 45 met the inclusion criteria. We identified three main categories of outcome measure specific to perioperative pulmonary outcomes: (i) composite outcome measures of multiple pulmonary outcomes (27 definitions); (ii) pneumonia (12 definitions); and (iii) respiratory failure (six definitions). These were rated by the group according to suitability for routine use. The majority of definitions were given a low score, and many were imprecise, difficult to apply consistently, or both, in large patient populations. A small number of highly rated definitions were identified as appropriate for widespread use. The group then recommended four outcome measures for future use, including one new definition. CONCLUSIONS: A large number of postoperative pulmonary outcome measures have been used, but most are poorly defined. Our four recommended outcome measures include a new definition of postoperative pulmonary complications, incorporating an assessment of severity. These definitions will meet the needs of most clinical effectiveness trials of treatments to improve postoperative pulmonary outcomes.

Difficult intubation in obese patients: incidence, risk factors, and complications in the operating theatre and in intensive care units.

BACKGROUND: Intubation procedure in obese patients is a challenging issue both in the intensive care unit (ICU) and in the operating theatre (OT). The objectives of the study were (i) to compare the incidence of difficult intubation and (ii) its related complications in obese patients admitted to ICU and OT. METHODS: We conducted a multicentre prospective observational cohort study in ICU and OT in obese (BMI≥30 kg m(-2)) patients. The primary endpoint was the incidence of difficult intubation. Secondary endpoints were the risk factors for difficult intubation, the use of difficult airway management techniques, and severe life-threatening complications related to intubation (death, cardiac arrest, severe hypoxaemia, severe cardiovascular collapse). RESULTS: In cohorts of 1400 and 11 035 consecutive patients intubated in ICU and in the OT, 282 (20%) and 2103 (19%) were obese. In obese patients, the incidence of difficult intubation was twice more frequent in ICU than in the OT (16.3% vs 8.2%, P<0.01). In both cohorts, risk factors for difficult intubation were Mallampati score III/IV, obstructive sleep apnoea syndrome, and reduced mobility of cervical spine, while limited mouth opening, severe hypoxaemia, and coma appeared only in ICU. Specific difficult airway management techniques were used in 66 (36%) cases of difficult intubation in obese patients in the OT and in 10 (22%) cases in ICU (P=0.04). Severe life-threatening complications were significantly more frequent in ICU than in the OT (41.1% vs 1.9%, relative risk 21.6, 95% confidence interval 15.4-30.3, P<0.01). CONCLUSIONS: In obese patients, the incidence of difficult intubation was twice more frequent in ICU than in the OT and severe life-threatening complications related to intubation occurred 20-fold more often in ICU. CLINICAL TRIAL REGISTRATION: Current controlled trials. Identifier: NCT01532063.

A multicentre observational study of intra-operative ventilatory management during general anaesthesia: tidal volumes and relation to body weight.

We conducted an observational prospective multicenter study to describe the practices of mechanical ventilation, to determine the incidence of use of large intra-operative tidal volumes (≥10 ml.kg(-1) of ideal body weight) and to identify patient factors associated with this practice. Of the 2960 patients studied in 97 anaesthesia units from 49 hospitals, volume controlled mode was the most commonly used (85%). The mean (SD) tidal volume was 533 (82) ml; 7.7 (1.3) ml.kg(-1) (actual weight) and 8.8 (1.4) ml.kg(-1) (ideal body weight)). The lungs of 381 (18%) patients were ventilated with a tidal volume>10 ml.kg(-1) ideal body weight. Being female (OR 5.58 (95% CI 4.20-7.43)) and by logistic regression, underweight (OR 0.06 (95% CI 0.01-0.45)), overweight (OR 1.98 (95% CI 1.49-2.65)), obese (OR 5.02 (95% CI 3.51-7.16)), severely obese (OR 10.12 (95% CI 5.79-17.68)) and morbidly obese (OR 14.49 (95% CI 6.99-30.03)) were the significant (p ≤ 0.005) independent factors for the use of large tidal volumes during anaesthesia.

[Preoperative risk and perioperative management of obese patients]. / Risque pré-opératoire et gestion péri-opératoire des patients obèses.

The obese patient is at an increased risk of perioperative complications. Most importantly, these include difficult access to the airways (intubation, difficult or impossible ventilation), and post-extubation respiratory distress secondary to the development of atelectasis or obstruction of the airways, sometimes associated with the use of morphine derivatives. The association of obstructive sleep apnea syndrome (OSA) with obesity is very common, and induces a high risk of peri- and postoperative complications. Preoperative OSA screening is crucial in the obese patient, as well as its specific management: use of continuous positive pre, per and postoperative pressure. For any obese patient, the implementation of protocols for mask ventilation and/or difficult intubation and the use of protective ventilation, morphine-sparing strategies and a semi-seated positioning throughout the care, is recommended, combined with close monitoring postoperatively. The dosage of anesthetic drugs should be based on the theoretical ideal weight and then titrated, rather than dosed to the total weight. Monitoring of neuromuscular blocking should be used where appropriate, as well as monitoring of the depth of anesthesia. The occurrence of intraoperative recall is indeed more frequent in the obese patient than in the non-obese patient. Appropriate prophylaxis against venous thromboembolic disease and early mobilization are recommended, as thromboembolic disease is increased in the obese patient. The use of non-invasive ventilation to prevent the occurrence of acute post-operative respiratory failure and for its treatment is particularly effective in obese patients. In case of admission to ICU, an individualized ventilatory management based on pathophysiology and careful monitoring should be initiated.

Hemoperitoneum in peripartum: A case-series.

Hemorrhages are the first cause of perinatal deaths in French women. Thirteen percent of these deaths are not linked to obstetrical problems but rather to hemoperitoneum. These incidents are under-diagnosed and as a result, treatment is delayed and fetal and maternal mortality increases. We report three cases of patients, all White female in their last trimester of a non-problematic pregnancy presenting with hemoperitoneum and resulting in different outcomes. The analysis of published materials and of our cases leads us to infer that a diagnosis of hemoperitoneum must be considered in pregnant women when abdominal pain, symptoms of shock and a decrease in hemoglobin are associated. An immediate response and intensive care followed by hemostatic surgery give these patients the best chance to survive.

Effects of clamping procedures on central venous pressure during liver resection.

BACKGROUND: Various clamping procedures are used to decrease bleeding during liver resections but their effect on central venous pressure (CVP) remains unclear. The aim of this study was to assess the variations of the CVP during two different clamping procedures. METHODS: We retrospectively reviewed 29 patients (19 males, 10 females) who had Pringle maneuver (PM) and clamping of the inferior vena cava below the liver (IVCC) during major liver resections. RESULTS: Mean decrease of the CVP after PM, IVCC, and PM+IVCC was 0.84 ± 1.37, 2.17 ± 2.13 and 3.17 ± 2.56 cmH20, respectively (P=0.02, P<0.0001 and P<0.0001, respectively). IVCC was more effective in inducing a decrease of the CVP than PM alone (P<0.05). The combination of both PM and IVCC induced the greatest decrease but not to a level of significance compared to IVCC alone (P=0.25). CONCLUSION: IVCC remains the more efficient procedure to lower the CVP. However, although PM is commonly used to control vascular inflow within the liver its significant influence on the CVP could participate to the reduction of bleeding during liver resections.

Protective lung ventilation in operating room: a systematic review.

Postoperative pulmonary and extrapulmonary complications adversely affect clinical outcomes and healthcare utilization, so that prevention has become a measure of the quality of perioperative care. Mechanical ventilation is an essential support therapy to maintain adequate gas exchange during general anesthesia for surgery. Mechanical ventilation using high tidal volume (VT) (between 10 and 15 mL/kg) has been historically encouraged to prevent hypoxemia and atelectasis formation in anesthetized patients undergoing abdominal and thoracic surgery. However, there is accumulating evidence from both experimental and clinical studies that mechanical ventilation, especially the use of high VT and plateau pressure, may potentially aggravate or even initiate lung injury. Ventilator-associated lung injury can result from cyclic alveolar overdistension of non-dependent lung tissue, and repetitive opening and closing of dependent lung tissue resulting in ultrastructural damage at the junction of closed and open alveoli. Lung-protective ventilation, which refers to the use of lower VT and limited plateau pressure to minimize overdistension, and positive end-expiratory pressure to prevent alveolar collapse at end-expiration, was shown to improve outcome in critically ill patients with acute respiratory distress syndrome (ARDS). It has been recently suggested that this approach might also be beneficial in a broader population, especially in critically ill patients without ARDS at the onset of mechanical ventilation. There is, however, little evidence regarding a potential beneficial effect of lung protective ventilation during surgery, especially in patients with healthy lungs. Although surgical patients are frequently exposed to much shorter periods of mechanical ventilation, this is an important gap in knowledge given the number of patients receiving mechanical ventilation in the operating room. This review developed the benefits of lung protective ventilation during surgery and general anesthesia and offers some recommendations for mechanical ventilation in the surgical context.

Non-invasive ventilation after surgery.

After surgery, hypoxemia and/or acute respiratory failure (ARF) mainly develop following abdominal and/or thoracic surgery. Anesthesia, postoperative pain and surgery will induce respiratory modifications: hypoxemia, pulmonary volumes decrease and atelectasis associated to a restrictif syndrome and a diaphragm dysfunction. Maintenance of adequate oxygenation in the postoperative period is of major importance, especially when pulmonary complications such as ARF occur. Although invasive endotracheal mechanical ventilation has remained the cornerstone of ventilatory strategy for many years for severe acute respiratory failure, several studies have shown that mortality associated with pulmonary disease is largely related to complications of postoperative reintubation and mechanical ventilation. Therefore, major objectives for anesthesiologists and surgeons are first to prevent the occurrence of postoperative complications and second if ARF occurs is to ensure oxygen administration and carbon dioxide CO2 removal while avoiding intubation. Non-invasive ventilation (NIV) does not require endotracheal tube or tracheotomy and its use is well established to prevent ARF occurrence (prophylactic treatment) or to treat ARF to avoid reintubation (curative treatment). Studies shows that patient-related risk factors, such as chronic obstructive pulmonary disease (COPD), age older than 60 years, American Society of Anesthesiologists ASA class of II or higher, obesity, functional dependence, and congestive heart failure, increase the risk for postoperative pulmonary complications. Rationale for postoperative NIV use is the same as the post-extubation NIV use plus the specificities due to the respiratory modifications induced by the surgery and anesthesia. Postoperative NIV improves gas exchange, decreases work of breathing and reduces atelectasis. The aims of this article are (1) to review the main respiratory modifications induced by surgery and anesthesia which justify postoperative NIV use (2) to offer some recommendations to apply safely postoperative NIV and (3) to present the main results obtained with preventive and curative NIV in a surgical context.

Mechanical ventilation in abdominal surgery.

One of the key challenges in perioperative care is to reduce postoperative morbidity and mortality. Patients who develop postoperative morbidity but survive to leave hospital have often reduced functional independence and long-term survival. Mechanical ventilation provides a specific example that may help us to shift thinking from treatment to prevention of postoperative complications. Mechanical ventilation in patients undergoing surgery has long been considered only as a modality to ensure gas exchange while allowing maintenance of anesthesia with delivery of inhaled anesthetics. Evidence is accumulating, however, suggesting an association between intraoperative mechanical ventilation strategy and postoperative pulmonary function and clinical outcome in patients undergoing abdominal surgery. Non-protective ventilator settings, especially high tidal volume (VT) (>10-12mL/kg) and the use of very low level of positive end-expiratory pressure (PEEP) (PEEP<5cmH2O) or no PEEP, may cause alveolar overdistension and repetitive tidal recruitment leading to ventilator-associated lung injury in patients with healthy lungs. Stimulated by previous findings in patients with acute respiratory distress syndrome, the use of lower tidal volume ventilation is becoming increasingly more common in the operating room. However, lowering tidal volume, though important, is only part of the overall multifaceted approach of lung protective mechanical ventilation. In this review, we aimed at providing the most recent and relevant clinical evidence regarding the use of mechanical ventilation in patients undergoing abdominal surgery.

How to choose an anesthesia ventilator?

During the past few years, many manufacturers have developed a new generation anesthesia ventilators or anesthesia workstations with innovative technology and introduced so-called new ventilatory modes in the operating room. The aim of this article is to briefly explain how an anesthesia ventilator works, to describe the main differences between the technologies used, to describe the main criteria for evaluating technical and pneumatic performances and to list key elements not to be forgotten during the process of acquiring an anesthesia ventilator.

How to preoxygenate in operative room: healthy subjects and situations "at risk".

Intubation is one of the most common procedures performed in operative rooms. It can be associated with life-threatening complications when difficult airway access occurs, in patients who cannot tolerate even a slight hypoxemia or when performed in patients at risk of oxygen desaturation during intubation, as obese, critically-ill and pregnant patients. To improve intubation safety, preoxygenation is a major technique, extending the duration of safe apnoea, defined as the time until a patient reaches an arterial saturation level of 88% to 90%, to allow for placement of a definitive airway. Preoxygenation consists in increasing the lung stores of oxygen, located in the functional residual capacity, and helps preventing hypoxia that may occur during intubation attempts. Obese, critically-ill and pregnant patients are especially at risk of reduced effectiveness of preoxygenation because of pathophysiological modifications (reduced functional residual capacity (FRC), increased risk of atelectasis, shunt). Three minutes tidal volume breathing or 3-8 vital capacities are recommended in general population, mostly allowing achieving a 90% end-tidal oxygen level. Recent studies have indicated that in order to maximize the value of preoxygenation (i.e, oxygenation stores) obese and critically-ill patients can benefit from the combination of breathing 100% oxygen and non-invasive positive pressure ventilation (NIV) with end-expiratory positive pressure (PEEP) in the proclive position (Trendelenburg reverse). Recruitment manoeuvres may be of interest immediately after intubation to limit the risk of lung derecruitment. Further studies are needed in the field of preoxygenation in pregnant women.

Lung imaging in patients with acute respiratory distress syndrome: from an understanding of pathophysiology to bedside monitoring.

Over the last 25 years, lung imaging has changed our understanding of acute respiratory distress syndrome. Alveolar recruitment, hyperinflation, and positive end-expiratory pressure-induced changes in lung aeration have become evaluable using CT, PET, and ultrasonography. The data have revealed that patients differ, in that the required ventilator settings vary in those with the same syndrome. At the bedside, however, care physicians remain blinded. Bedside tools allowing monitoring of mechanical ventilation, and testing of ventilator settings, are urgently required. The aim of the present review is to consider how lung imaging has facilitated the evolution of knowledge of this syndrome, and to place such knowledge in a clinical perspective.

Comparison of three high flow oxygen therapy delivery devices: a clinical physiological cross-over study.

AIM: High-flow-oxygen-therapy is provided by various techniques and patient interfaces, resulting in various inspired-fraction of oxygen (FiO2) and airway-pressure levels. However, tracheal measurements have never been performed. METHODS: Three oxygen-delivery-devices were evaluated: 1) standard-high-flow-oxygen-facemask with reservoir-bag, 2) Optiflow(TM)-high-flow-nasal-cannulae and 3) Boussignac(TM)-oxygen-therapy-system. Main judgment criteria were airway-pressure and FiO2 measured in the trachea. The three devices were randomly evaluated in cross-over in 10 Intensive-Care-Unit patients using three oxygen flow-rates (15, 30 and 45 L/min) and two airway-tightness conditions (open and closed mouth). Airway-pressures and FiO2 were measured by a tracheal-catheter inserted through the hole of a tracheotomy tube. Comfort was evaluated by self-reporting. Data are presented as median [25-75th]. RESULTS: 1) Regarding oxygen-delivery devices, BoussignacTM provided the highest mean tracheal pressure (13.9 [10.4-14.5] cmH20) compared to Optiflow(TM) (2 [1-2.3] cmH2O, P<0.001). BoussignacTM provided both positive inspiratory and expiratory airway-pressures, whereas Optiflow(TM) provided only positive expiratory airway-pressure. Reservoir-bag-facemask provided airway pressure close to zero. For FiO2, highest value was obtained for both Optiflow(TM) and facemask (90%) compared to Boussignac(TM) (80%), P<0.01. 2) Regarding oxygen-flow, airway-pressure and FiO2 systematically increased with oxygen-flow with the three devices except airway-pressure for the facemask. 3) Regarding the open-mouth position, mean airway-pressure decreased with Optiflow(TM) only (2 [1.2-3.3] vs. 0.6 [0.3-1] cmH2O, P<0.001). Opening the mouth had little impact on FiO2. 4) finally, discomfort-intensities were low for both Optiflow(TM) and reservoir-bag-facemask compared to Boussignac(TM), P<0.01. CONCLUSION: On one hand, Boussignac(TM) is the only device that generates a relevant positive-airway-pressure during both inspiration-and-expiration, independently of mouth-position. Optiflow(TM) provides a low positive-airway-pressure (<4 cmH2O), highly dependent of mouth-closing. The reservoir-bag-facemask provides no positive-airway-pressure. On the other hand, FiO2 are slightly but significantly higher for Optiflow(TM) and reservoir-bag-facemask than for Boussignac(TM). Discomfort was lesser for Optiflow(TM) and reservoir-bag-facemask.

Influence of opioid choice on mechanical ventilation duration and ICU length of stay.

BACKGROUND: The aim of this study was to assess the impact on mechanical ventilation and ICU outcomes of substituting remifentanil for sufentanil, in an analgesia-based sedation protocol. A database of data prospectively collected was retrospectively analyzed. The study was carried out in a 16-bed tertiary-care ICU. METHODS: The study included 1544 mechanically ventilated patients admitted from January 2001 to December 2006. Patients were compared between two consecutive phases. Analgesia-based sedation guidelines were the same, except for the opiate used. The patient-to-nurse ratio (2.5) and ventilator weaning practices remained unchanged. 794 patients were included during the sufentanil phase, and 750 during the remifentanil phase. Remifentanil was associated with significantly less time spent on mechanical ventilation (10 days[3-21] vs. 14 days[3-27], P<0.01) and in the ICU (16 days[3-22] vs. 19 days[4-26], P<0.01). The difference was significant for patients ventilated no longer than four days (P=0.0035) but not for patients ventilated more than four days (P=0.058). Sedation target on the Ramsay scale was reached more often with remifentanil. The use and amount of hypnotic agents in addition to the opiate were significantly lower with remifentanil. The cost of analgesia-based sedation was similar in the sufentanil and the remifentanil group. CONCLUSION: Our study suggests that using a short-acting opiate with short context-sensitive half-life in an analgesia-based sedation protocol may significantly decrease the duration of mechanical ventilation and the ICU length of stay even though not significantly in long term sedation, while improving the achievement of sedation goals despite a lower requirement for adjunctive hypnotic agents, with no additional costs.