Hepatopulmonary Syndrome and Post-Liver Transplantation Complications: A Case-Control Study.

BACKGROUND: Although liver transplantation (LT) improves survival in cirrhotic patients with hepatopulmonary syndrome (HPS), few data exist concerning post-operative complications in these patients. OBJECTIVE: To compare complications after LT between patients with and without HPS. METHODS: In a case-control study, we retrospectively analyzed all patients who underwent LT in our center from January 2010 to July 2016. We compared cases of identified HPS to controls matched for age, MELD score, comorbidities, red blood cells transfused, and highest dosage of norepinephrine perfused during transplantation. RESULTS: Among 451 transplanted patients, we identified 71 patients with HPS who could be analyzed. We found a significantly (p<0.001) higher number of post-operative complications in patients with HPS (median 5 vs 3), with more occurrence of cardiac, infectious and surgical complications than in the controls: 39.4% vs 12.7% (p<0.001), 81.7% vs 49.3% (p<0.001), and 59.2% vs 40.1% (p<0.029), respectively. There were also more ICU readmissions at 1 month among HPS patients (10 vs 1, p=0.01). There was no significant difference concerning ventilation data, lengths of ICU or hospital stay (8.5 [range 3-232] and 32 [14-276] days, respectively on the whole cohort) and death in the ICU (4.2% on the whole cohort). The 1-year survival was higher in HPS patients (94.4% vs 81.1%, p=0.034); there was no difference in 5-year survival. CONCLUSION: HPS patients seem to have a higher number of complications in the first month following LT.

Surgical activity during the Covid-19 pandemic: Results for 112 patients in a French tertiary care center, a quality improvement study.

BACKGROUND: After the emergence of Covid-19 in China, Hubei Province, the epidemic quickly spread to Europe. France was quickly hit and our institution was one of the first French university to receive patients infected with Sars-COV2. The predicted massive influx of patients motivated the cancellation of all elective surgical procedures planned to free hospitalization beds and to free intensive care beds. Nevertheless, we should properly select patients who will be canceled to avoid life-threatening. The retained surgical indications are surgical emergencies, oncologic surgery, and organ transplantation. MATERIAL AND METHODS: We describe the organization of our institution which allows the continuation of these surgical activities while limiting the exposure of our patients to the Sars Cov2. RESULTS: After 4 weeks of implementation of intra-hospital protocols for the control of the Covid-19 epidemic, 112 patients were operated on (104 oncology or emergency surgeries and 8 liver transplants). Only one case of post-operative contamination was observed. No mortality related to Covid-19 was noted. No cases of contamination of surgical care personnel have been reported. CONCLUSION: We found that the performance of oncological or emergency surgery is possible, safe for both patients and caregivers.

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.

Use of analgesics in France, following dextropropoxyphene withdrawal.

BACKGROUND: In 2009, the European Medicines Agency recommended withdrawal of dextropropoxyphene (DXP); in March 2011 it was withdrawn from the market in France. Up until that time the combination dextropropoxyphene-paracetamol (DXP/PC) was widely used for analgesia. At withdrawal, French regulators recommended that DXP/PC be replaced by other step 2 analgesics, i.e. tramadol, codeine, or opium-containing drugs, or by PC for a weak level of pain. To investigate prescribing behaviours after DXP/PC withdrawal, dispensations of analgesics before and after withdrawal were analysed. METHODS: Aggregated dispensation data of analgesics prescribed between January 2009 and December 2012 in the Rhône-Alpes region were obtained from the general health insurance claims data; changes in analgesic dispensation over time were analysed with the ATC/DDD methodology. Pre (Jan-June 2009) and post-withdrawal (Jan-June 2012) changes of DDDs where computed for each analgesic step. RESULTS: The dispensations of DXP/PC experienced a two-step decrease until 2011. Over the withdrawal period 2009-2012, there was a 14% decrease in the overall use of analgesic (from 109 to 94 DDDs), while the use of step 2 analgesics declined by 46% (- 22 DDDs, from 47 to 25 DDDs). This latter decline included a cessation of use of DXP/PC (29 DDDs in 2009) that were only in part (+ 7 DDDs, from 18 to 25 DDDs) compensated by increased use of codeine, tramadol and opium, in monotherapy or combined with PC. For step 1 analgesics, use increased with 9%, mostly PC (+ 8 DDDs, from 31 to 39 DDDs). Step 3 analgesics dispensations remained largely unchanged over this period (around 3 DDDs). CONCLUSIONS: In the Rhône-Alpes region, DXP/PC withdrawal was accompanied in part by an increased use of same level analgesics, and in part by an increased use of PC in monotherapy. The extent of DXP/PC use before withdrawal, and the increased use of PC after DXP withdrawal, underline the complexity of pain management.

A systematic review of interventions and performance measures for antifungal stewardship programmes.

Objectives: Antifungal resistance is a significant and emerging threat. Stewardship programmes (SPs) have been proposed as an opportunity to optimize antifungal use. While examples of antifungal SP implementation have been recently described, there is yet to be an overview of interventions and their impacts on performance measures. Methods: We systematically reviewed published articles using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses check-list 2009. MEDLINE was searched using the term 'antifungal stewardship' on 15 February 2017. Eligible studies were those that described an antifungal SP and included an intervention and an evaluation of performance measures. Results: A total of 97 studies were identified and 14 were included. Only five studies reported an antifungal stewardship team composed of all the recommended members. The main intervention was the formulation of recommendations to change treatment (12 of 14). The main performance measure collected was antifungal consumption (10 of 14), followed by antifungal expenditure (7 of 14), adherence to therapeutic advice (4 of 14) and impact on mortality (4 of 14). Antifungal consumption was reduced by 11.8% to 71% and antifungal expenditure by as much as 50%. Adherence to therapeutic advice ranged from 40% to 88%, whereas antifungal SPs had no impact on mortality. Conclusions: All antifungal SPs had an impact, in particular on antifungal consumption and antifungal expenditure. Active intervention including a review of prescriptions seems to have more impact than implementation of treatment guidelines only. According to available published studies, antifungal consumption appears to be the most achievable performance measure to evaluate the impact of an antifungal SP.

What are the therapeutic alternatives to dextropropoxyphene in France? A prescribers' survey.

About a year after dextropropoxyphene (DXP) withdrawal from the French market, we conducted a survey among members of the French Society of Anesthesia & Intensive Care Medicine (Sfar) and of the French Society of the Study and Treatment of Pain (SFETD) to identify the indications for which this WHO level II analgesic had been prescribed, the prescriber's feedback following withdrawal, and the substitutive analgesics prescribed. DXP had been prescribed by more than 75% of the 430 anaesthesiologists and 230 pain specialists interviewed, mainly for acute and chronic non-cancer pain of moderate intensity. While two thirds of pain specialists were not satisfied with DXP withdrawal, this decision did not affect the majority of anaesthesiologists. In both groups, the main substitutive analgesic was tramadol combined with acetaminophen, while only 24% of prescribers considered acetaminophen alone as a substitute.

[Medication errors with concentrated potassium intravenous solutions: Data of the literature, context and prevention]. / Erreurs médicamenteuses avec les solutés concentrés de potassium injectable: données de la littérature, état des lieux et prévention.

Accidental direct intravenous injection of a concentrated solution of potassium often leads to patient death. In France, recommendations of healthcare agencies to prevent such accidents cover only preparation and intravenous infusion conditions. Accidents continue to occur in French hospitals. These facts demonstrate that these recommendations are insufficient and ineffective to prevent such deaths, especially those occurring during a catheter flushing. This article reviews the measures able to reduce the number of accidents. Countries which removed concentrated ampoules from ward stocks observed a decrease of the number of accidental deaths. This withdrawal, recommended by the World Health Organization, is now part of standards in studies aimed at determining the safety of care in hospitals. However, removal alone is insufficient to eliminate the risk. The combination with other measures should be considered. These measures are the provision of a combination of diluted intravenous ready to use solutions, the promotion of the oral route with tablets and oral solutions for potassium replenishment and to make available products with safeguards to prevent single shot intravenous injection. Studies aimed at determining the consequences on preventing concentrated potassium accidents of a widespread distribution of isotonic sodium chloride pre-filled ready-to-use syringes for catheter flushing should be performed.

The influence of various reef sounds on coral-fish larvae behaviour.

The swimming behaviour of coral-reef fish larvae from 20 species of 10 different families was tested under natural and artificial sound conditions. Underwater sounds from reef habitats (barrier reef, fringing reef and mangrove) as well as a white noise were broadcasted in a choice chamber experiment. Sixteen of the 20 species tested significantly reacted to at least one of the habitat playback conditions, and a range of responses was observed: fishes were (1) attracted by a single sound but repelled by none (e.g. white-banded triggerfish Rhinecanthus aculeatus was attracted by the barrier-reef sound), (2) repelled by one or more sounds but attracted by none (e.g. bridled cardinalfish Pristiapogon fraenatus was repelled by the mangrove and the bay sounds), (3) attracted by all sounds (e.g. striated surgeonfish Ctenochaetus striatus), (4) attracted and repelled by several sounds (e.g. whitetail dascyllus Dascyllus aruanus was attracted by the barrier-reef sound and repelled by the mangrove sound) and (5) not influenced by any sound (e.g. convict surgeonfish Acanthurus triostegus). Overall, these results highlight two settlement strategies: a direct selection of habitats using sound (45% of the species), or a by-default selection by avoidance of certain sound habitats (35%). These results also clearly demonstrated the need to analyse the influence of sounds at the species-specific level since congeneric and confamilial species can express different behaviours when exposed to the same sounds.

[Cerebral aspergillosis and liver transplantation: about one case]. / Aspergillose cérébrale et transplantation hépatique: discussion autour d'un cas.

Cerebral invasive aspergillosis is a rare but serious infection. Mortality is still high despite appropriate treatment. We report the case of a patient with liver transplantation in the context of alcoholic cirrhosis and transplanted back seven years later consequently to an ischemic cholangitis. Following an acquired active viral infection by HCV and treated by antiviral combination therapy the patient presented six months after this second operation a cerebral aspergillosis of tumour-like presentation. It rapidly evolved to an unfavourable outcome with intracranial hypertension state. If the therapeutic management is well established, the diagnosis is difficult. This observation allows us to discuss the various diagnostic criteria of cerebral aspergillosis.

[Postoperative intravenous morphine titration in PACU after bariatric laparoscopic surgery]. / Titration morphinique intraveineuse en salle de surveillance post-interventionnelle (SSPI) après chirurgie bariatrique sous cœlioscopie.

OBJECTIVE: There is limited information available regarding intravenous (IV) morphine administration in obese patients in PACU. The aim of this study was to compare two IV morphine titration (IMT) regimen in two surgical centers. STUDY DESIGN: Observational study. PATIENTS: Laparoscopic bariatric surgery in one private (Saint-Grégoire Clinic) and one public (University Hospital of Amiens) surgical center. METHODS: A strict and common protocol of IMT was implemented if PACU of both centers according to the recommendations of the French Society of Anaesthesia and Intensive Care. When pain score increased to>30, IMT was titrated every 5 min in 3mg increments until pain relief (VAS≤30 mm). Pain level, dose of morphine (per total and ideal body weight), effectiveness, and side events were recorded. RESULTS: Data were recorded for 159 adult patients (129 women). Mean age and BMI were 42±12 yrs and 43.8±6.9 kg/m(2). Ninety-eight patients were eligible for IMT regimen but only 76 patients received IV morphine (47.8 %). Mean dose was 7.3 mg±3.5mg [1-19 mg], (60.4 µg/kg and 115.8 µg/kg). IMT was less frequent, mean dose was greater (8.6±4.2 vs 6.2±2.9 mg) and number of patients with pain relief was higher (73.7 vs 35.6 %) in the public hospital. No severe adverse events have been recorded and there was no difference in both centers regarding these events. CONCLUSION: Implementation of a IMT regimen in PACU was not associated with effective pain relief after laparoscopic surgery in obese patients.

An attempt to validate the modification of the American-European consensus definition of acute lung injury/acute respiratory distress syndrome by the Berlin definition in a university hospital.

PURPOSE: The Berlin definition for acute respiratory distress syndrome (ARDS) is a new proposal for changing the American-European consensus definition but has not been assessed prospectively as yet. In the present study, we aimed to determine (1) the prevalence and incidence of ARDS with both definitions, and (2) the initial characteristics of patients with ARDS and 28-day mortality with the Berlin definition. METHODS: We performed a 6-month prospective observational study in the ten adult ICUs affiliated to the Public University Hospital in Lyon, France, from March to September 2012. Patients under invasive or noninvasive mechanical ventilation, with PaO2/FiO2 <300 mmHg regardless of the positive end-expiratory pressure (PEEP) level, and acute onset of new or increased bilateral infiltrates or opacities on chest X-ray were screened from ICU admission up to discharge. Patients with cardiogenic pulmonary edema were excluded. Patients were further classified into specific categories by using the American-European Consensus Conference and the Berlin definition criteria. The complete data set was measured at the time of inclusion. Patient outcome was measured at day 28 after inclusion. RESULTS: During the study period 3,504 patients were admitted and 278 fulfilled the American-European Consensus Conference criteria. Among them, 18 (6.5 %) did not comply with the Berlin criterion PEEP ≥ 5 cmH2O and 20 (7.2 %) had PaO2/FiO2 ratio ≤200 while on noninvasive ventilation. By using the Berlin definition in the remaining 240 patients (n = 42 mild, n = 123 moderate, n = 75 severe), the overall prevalence was 6.85 % and it was 1.20, 3.51, and 2.14 % for mild, moderate, and severe ARDS, respectively (P > 0.05 between the three groups). The incidence of ARDS amounted to 32 per 100,000 population per year, with values for mild, moderate, and severe ARDS of 5.6, 16.3, and 10 per 100,000 population per year, respectively (P < 0.05 between the three groups). The 28-day mortality was 35.0 %. It amounted to 30.9 % in mild, 27.9 % in moderate, and 49.3 % in severe categories (P < 0.01 between mild or moderate and severe, P = 0.70 between mild and moderate). In the Cox proportional hazard regression analysis ARDS stage was not significantly associated with patient death at day 28. CONCLUSIONS: The present study did not validate the Berlin definition of ARDS. Neither the stratification by severity nor the PaO2/FiO2 at study entry was independently associated with mortality.

[Peripartum period and hemophilia carriers]. / Gestion du péri-partum de la patiente conductrice d'une hémophilie.

Women who are carriers for hemophilia are usually considered as safe carriers. However, they can present hemorragic symptoms associated with low factor VIII or IX levels. During pregancy, factor VIII increases whereas factor IX does not. The peripartum period is at risk of increased bleeding in these women. Here are presented reports of clinical data concerning two hemophilia carriers with low factor VIII or IX (30-40%) during the peripartum period. They received remifentanil and ketamine for labor pain management because of contraindication of epidural and spinal analgesia. Delivery occured quickly but they presented immediate moderate postpartum haemorrage. They did not necessitate blood transfusion. The one with hemophilia A received desmopressin just after delivery and the other one received factor IX when she arrived in delivery room. Blood factor VIII or IX has to be assessed in these women with familial history of hemophilia and bleeding. During pregnancy, factor VIII increases and can be assessed many times during pregnancy expecting a level over 50%. Factor IX does not really increase during pregancy and hemorrage can occur. Epidural and spinal anesthesia seem to be contraindicated as far as recommandations are concerned. Coagulation factor substitution is a mean of increasing factor level before these anaesthesias and can be discussed for each case.

Prescriptions analysis by clinical pharmacists in the post-operative period: a 4-year prospective study.

BACKGROUND: Clinical pharmacists can help prevent medication errors. However, data are scarce on their role in preventing medication prescription errors in the post-operative period, a high-risk period, as at least two prescribers can intervene, the surgeon and the anesthetist. We aimed to describe and quantify clinical pharmacist' intervention (PIs) during validation of drug prescriptions on a computerized physician order entry system in a post-surgical and post-transplantation ward. We illustrate these interventions, focusing on one clearly identified recurrent problem. METHODS: In a prospective study lasting 4 years, we recorded drug-related problems (DRPs) detected by pharmacists and whether the physician accepted the PI when prescription modification was suggested. RESULTS: Among 7005 orders, 1975 DRPs were detected. The frequency of PIs remained constant throughout the study period, with 921 PIs (47%) accepted, 383 (19%) refused and 671 (34%) not assessable. The most frequent DRP concerned improper administration mode (26%), drug interactions (21%) and overdosage (20%). These resulted in a change in the method of administration (25%), dose adjustment (24%) and drug discontinuation (23%) with 307 drugs being concerned by at least one PI. Paracetamol was involved in 26% of overdosage PIs. Erythromycin as prokinetic agent, presented a recurrent risk of potentially severe drug-drug interactions especially with other QT interval-prolonging drugs. Following an educational seminar targeting this problem, the rate of acceptation of PI concerning this DRP increased. CONCLUSION: Pharmacists detected many prescription errors that may have clinical implications and could be the basis for educational measures.

Evaluation of perioperative risk in elderly patients.

From a medical point of view, aging is characterized by a potential failure to maintain homeostasis under conditions of physiological stress. This failure is associated with an increase in vulnerability. Physiological changes associated with aging are progressive but concomitant injury or diseases may rapidly worsen the health status of the patient. Increasing age independently predicts morbidity and mortality. Hypertension and dyspnea are probably two of the most frequent risk factors in elderly patients. The history of the elderly patient should assess functional status, including cardiovascular reserve sufficient to withstand very stressful operations. The type of surgery has important implications for perioperative risk and emergency surgery, particularly in the elderly, is associated with a high risk of morbidity. Elderly patients who are otherwise acceptable surgical candidates should not be denied surgery based solely on their age and concerns for postoperative renal, cardiovascular, cognitive or pulmonary complications. Renal impairment becomes more prevalent with advancing age as the glomerular filtration rate decreases. The surgical site is the single most important predictor of pulmonary complications. Concerning postoperative comfort and neurological complications, age is the highest risk factor for developing dementia. Pain is underassessed and undermanaged. The elderly are at higher risk of adverse consequences from unrelieved or undertreated pain.

[Wound infiltration with local anesthetics for postoperative analgesia. Results of a national survey about its practice in France]. / Infiltrations d'anesthésiques locaux pour l'analgésie postopératoire chez l'adulte. Résultats d'une enquête nationale de pratique.

BACKGROUND AND OBJECTIVE: Local wound infiltration is a component of multimodal postoperative (p.o.) analgesia. Its implementation in current clinical practice remains unknown. Pain and Regional Anesthesia Committee of the French Anaesthesia and Intensive Care Society (Sfar) aimed to appraise its practice. METHOD: Postal sample survey based on representative sample of national activity were sent to heads of anaesthesiology departments. The questionnaires included 36 items on single-shot and continuous wound infiltrations (CWI) with considerations about modality of administration, drugs and development limitations. Results in mean [CI95 %]. RESULTS: Response rate was 32 % (n=120). Sample was in accordance with national representation of health institutions. Local infiltration was included in 85 % [79-91] of the p.o. analgesia protocols. Regardless of the surgery, single-shot wound infiltration and CWI were used in more than 50 % of the patients by respectively 58 % [49-67] and 18 % [11-25] of the responders. However, a significant part of the surgeons remained reluctant to CWI. Lack of information and fear of septic complications were the most reported barriers. Peritoneal instillation after laparoscopy was rarely performed, in contrast with intra-articular infiltration after knee arthroscopy, performed systematically or very frequently by 60 % [50-70] of the responders. CONCLUSION: The practice of local wound infiltration for p.o. analgesia seems presently well established, especially for single-shot injections. CWI is less commonly performed. Several surgical reluctances remain to be overcome. Better information about effectiveness and safety are likely to still improve their practices.

Postoperative intravenous morphine titration.

Relief of acute pain during the immediate postoperative period is an important task for anaesthetists. Morphine is widely used to control moderate-to-severe postoperative pain and the use of small i.v. boluses of morphine in the post-anaesthesia care unit allows a rapid titration of the dose needed for adequate pain relief. The essential principle of a titration regimen must be to adapt the morphine dose to the pain level. Although morphine would not appear to be the most appropriate choice for achieving rapid pain relief, this is the sole opioid assessed in many studies of immediate postoperative pain management using titration. More than 90% of the patients have pain relief using a protocol of morphine titration and the mean dose required to obtain pain relief is 12 (7) mg, after a median of four boluses. Sedation is frequent during i.v. morphine titration and should be considered as a morphine-related adverse event and not evidence of pain relief. The incidence of ventilatory depression is very low when the criteria to limit the dose of i.v. morphine are enforced. Morphine titration can be used with caution in elderly patients, in children, or in obese patients. In practice, i.v. morphine titration allows the physician to meet the needs of individual patients rapidly and limits the risk of overdose making this method the first step in postoperative pain management.