Hydroxychloroquine lung pharmacokinetics in critically ill patients with COVID-19.

Different dosage regimens of hydroxychloroquine (HCQ) have been used to manage COVID-19 (coronavirus disease 2019) patients, with no information on lung exposure in this population. The aim of our study was to evaluate HCQ concentrations in the lung epithelial lining fluid (ELF) in patients infected with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the virus that causes COVID-19. This was a retrospective, observational, multicentre, pharmacokinetic study of HCQ in critically ill COVID-19 patients. No additional interventions or additional samples compared with standard care of these patients were conducted in our teaching hospital. We included all intubated COVID-19 patients treated with crushed HCQ tablets, regardless of the dosage administered by nasogastric tube. Blood and bronchoalveolar lavage samples (n = 28) were collected from 22 COVID-19 patients and total HCQ concentrations in ELF were estimated. Median (interquartile range) HCQ plasma concentrations were 0.09 (0.06-0.14) mg/L and 0.07 (0.05-0.08) mg/L for 400 mg × 1/day and 200 mg × 3/day, respectively. Median HCQ ELF concentrations were 3.74 (1.10-7.26) mg/L and 1.81 (1.20-7.25) for 400 mg × 1/day and 200 mg × 3/day, respectively. The median ratio of ELF/plasma concentrations was 40.0 (7.3-162.7) and 21.2 (18.4-109.5) for 400 mg × 1/day and 200 mg × 3/day, respectively. ELF exposure is likely to be underestimated from HCQ concentrations in plasma. In clinical practice, low plasma concentrations should not induce an increase in drug dosage because lung exposure may already be high.

Clinical characteristics and outcome of hospitalized patients with SARS-CoV-2 infection at Toulouse University hospital (France). Results from the Covid-clinic-Toul cohort.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread worldwide from epicenter of Wuhan, China since December 2019. The aim of our study was to describe the clinical characteristics and outcome of hospitalized patients with SARS-CoV-2 pneumonia at the Toulouse university hospital, France. PATIENTS AND METHODS: We selected the patients included from March 7, 2020 to April 20, 2020 in the retrolective Covid-clinic-Toul cohort that follows all hospitalized patients with SARS-CoV-2 infection at the Toulouse Hospital. Cases were confirmed by real-time reverse transcriptase polymerase chain reaction. We report demographics, clinical, biological and radiological features, as well as unfavorable outcome at Day 14 after admission (admission in an intensive care unit, mechanical ventilation, death). RESULTS: Among 263 hospitalized patients, the median age was 65 years and 155 (58.9%) were males. Two hundred and twenty-seven patients (86.3%) had at least one comorbidity. The median time from first symptom to hospital admission was 7.0 days (interquartile range: 4-10). On day 14 after admission, 111 patients (42.2%) had been transferred to intensive care unit (ICU), including 50 (19.0%) on Day 1; 61 (23.1%) needed mechanical ventilation and 19 patients (7.2%) had died. Patients admitted to ICU at Day 1 of admission (n=50) were more frequently men (66.0% vs 57.3%), smokers (25.0% vs 7.1%), with obesity (42.0% vs 24.7%) and had a higher mean level of C-reactive protein (median: 110.9mg/L vs 46.2mg/L). CONCLUSION: This cohort provides epidemiological data on SARS-CoV-2 in hospitalized patients in a University hospital in the South of France.

Comparison of intubating conditions after induction with propofol and remifentanil or sufentanil : Randomized controlled REMIDENT trial for surgical tooth extraction.

PURPOSE: The aim of this study was to compare tracheal intubation conditions after induction of anesthesia with a bolus of propofol-sufentanil or propofol-remifentanil and a rapid induction technique. MATERIAL AND METHODS: A total of 70 patients (American Society of Anesthesiologists (ASA) classification I­II) undergoing outpatient surgery under general anesthesia with intubation for tooth extraction were randomly assigned to two groups in this double-blind study. Patients received either a bolus of remifentanil (3 µg/kg) or sufentanil (0.3 µg/kg) together with 2.5 mg/kg propofol for intubation. The primary outcome was the percentage of excellent intubation conditions and the secondary outcomes were the percentage of patients with a decrease of over 20% in mean arterial pressure (MAP) or heart rate (HR), time to achieve spontaneous respiration, time between the end of surgery and extubation and time to achieve an Aldrete score of 10. VAS pain score was >3 or having laryngeal pain 15 min after arriving in the postanesthesia care unit (PACU) were also analyzed. RESULTS: Intubating conditions (perfect + good conditions) were significantly better with remifentanil than with sufentanil (88.5% vs. 68.6%; p = 0.01). When using remifentanil, the hemodynamic conditions were good. Using remifentanil did not significantly increase the pain score or the laryngeal pain in the recovery room. This was confirmed by no significant differences between the groups for morphine consumption. Remifentanil significantly decreased the time to achieve an Aldrete score of 10. CONCLUSION: When intubation without muscle relaxants is required, intubating conditions are much better when a remifentanil bolus is used compared to a sufentanil bolus. The remifentanil/propofol rapid induction technique is a valuable technique to quickly intubate and achieve good conditions.

Hemidiaphragmatic paralysis following ultrasound-guided anterior vs. posterior suprascapular nerve block: a double-blind, randomised control trial.

Interscalene brachial plexus block provides analgesia for shoulder surgery but is associated with hemidiaphragmatic paralysis. Before considering a combined suprascapular and axillary nerve block as an alternative to interscalene brachial plexus block, evaluation of the incidence of diaphragmatic dysfunction according to the approach to the suprascapular nerve is necessary. We randomly allocated 84 patients undergoing arthroscopic shoulder surgery to an anterior or a posterior approach to the suprascapular nerve block combined with an axillary nerve block using 10 ml ropivacaine 0.375% for each nerve. The primary outcome was the incidence of hemidiaphragmatic paralysis diagnosed by ultrasound. Secondary outcomes included: characterisation of the hemidiaphragmatic paralysis over time; numeric rating scale pain scores; oral morphine equivalent consumption; and patient satisfaction. The incidence of hemidiaphragmatic paralysis was 40% (n = 17) vs. 2% (n = 1) in the anterior and posterior groups, respectively (p < 0.001). In one third of patients with hemidiaphragmatic paralysis, it persisted beyond the eighth hour. The median (interquartile range [range]) oral morphine equivalent consumption was significantly higher in the posterior approach when compared with the anterior approach, whether in the recovery area (20 [5-31 (0-60)] mg vs. 7.5 [0-14 (0-52)] mg, respectively; p = 0.004) or during the first 24 h (82 [61-127 (12-360) mg] vs. 58 [30-86 (0-160)] mg, respectively; p = 0.01). Patient satisfaction was comparable between groups (p = 0.6). Compared with the anterior approach, diaphragmatic function is best preserved with the posterior needle approach to the suprascapular nerve block.

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.

3-month prognostic impact of severe acute renal failure under veno-venous ECMO support: Importance of time of onset.

PURPOSE: Veno-venous ECMO is increasingly used for the management of refractory ARDS. In this context, acute kidney injury (AKI) is a major and frequent complication, often associated with poor outcome. We aimed to identify characteristics associated with severe renal failure (Kidney Disease Improving Global Outcome (KDIGO) 3) and its impact on 3-month outcome. METHODS: Between May 2009 and April 2016, 60 adult patients requiring VV-ECMO in our University Hospital were prospectively included. RESULTS: AKI occurrence was frequent (75%; n=45), 51% of patients (n=31) developed KDIGO 3 - predominantly prior to ECMO insertion - and renal replacement therapy was required in 43% (n=26) of cases. KDIGO 3 was associated with a lower mechanical ventilation weaning rate (24% vs 68% for patients with no AKI or other stages of AKI; p<0.001) and a higher 90-day mortality rate (72% vs 32%, p=0.002). Multivariate logistic regression suggested that KDIGO 3 occurrence prior to ECMO insertion, as well as PaCO2>57mmHg and mSOFA>12 were independent risks factors for 90-day mortality. CONCLUSION: KDIGO 3 AKI occurrence is correlated with the severity of patients' clinical condition prior to ECMO insertion and is negatively associated with 90-day survival.

Influence of Age on Decision-Making Process to Limit or Withdraw Life-Sustaining Treatment in the Intensive Care Unit - A Single Center Prospective Observational Study.

BACKGROUND: The increasing age in the industrialized countries places significant demands on intensive care unit (ICU) resources and this triggers debates about end-of-life care for the elderly. OBJECTIVES: We sought to determine the impact of age on the decision-making process to limit or withdraw life-sustaining treatment (DWLST) in an ICU in France. We hypothesized that there are differences in the decision-making process for young and old patients. DESIGN, SETTING, PARTICIPANTS: We prospectively studied end-of-life decision-making for all consecutive admissions (n=390) to a tertiary care university ICU in Toulouse, France over a period of 11 months between January and October 2011. RESULTS: Among the 390 patients included in the study (age ≥70yo, n=95; age <70yo, n=295) DWLST were more common for patients 70 years or older (43% for age ≥70yo vs. 16% for age <70yo, p <0.0001). Reasons for DWLST were different in the 2 groups, with the 'no alternative treatment options' and 'severity of illness' as the most frequent reasons cited for the younger group whereas it was 'severity of illness' for the older group. 'Advanced age' led to DWLSTs in 43% of the decisions in the group ≥70yo (vs. 0% in the group <70yo, p <0.0001). Multivariate logistic regression showed a high SAPS II score and age ≥70yo as independent risk factors for DWLSTs in the ICU. We did not find age ≥70yo as an independent risk factor for mortality in ICU. CONCLUSION: We found that age ≥70yo was an independent risk factor for DWLSTs for patients in the ICU, but not for their mortality. Reasons leading to DWLSTs are different according to the age of patients.

Can We Predict Morbidity and Mortality of Patients Aged 75 Years and Older Undergoing Cystectomy?

Radical cystectomy is associated with a high postoperative mortality and morbidity in older patients. We aimed to define the predictive value of comorbidity scores and determine the prognostic factors of postoperative complications. Preoperative associated morbidities were collected and graded according to the American Society of Anesthesiologists (ASA) score system, the Adult Comorbidity Evaluation (ACE) scale and the Charlson comorbidity index. Surgical complications were graded according to Clavien classification. Early and late complications were recorded. Data are from 49 consecutive patients aged ≥ 75 years who had an open surgery for bladder cancer. The most commonly associated conditions were smoking, renal insufficiency, and arterial hypertension. Incidence of early and late complications was 49% and 16%, respectively. Four and 25 death events occurred during the early and late follow-up, respectively. The incidence of morbidity and mortality were not related to ASA, ACE or Charlson scores. Preoperative malnutrition, renal insufficiency, higher need of perioperative blood transfusions, and prolonged ileus were identified as risk factors of postoperative morbidity. Late complications seemed related to low weight.

[Out-of-hospital equipment of emergency medical services for hemorrhagic shock management: can do better!]. / Équipement des Smur pour la prise en charge préhospitalière du choc hémorragique : peut mieux faire !

INTRODUCTION: Hemorrhagic shock is an emergency, which may benefit from a medicalized prehospital care. Our goal was to survey the means available in the 370 French prehospital medicalized emergency services (SMUR) for hemorrhagic situations. METHODS: Multicenter descriptive observational study by email then phone with all the 370 French SMUR leaders. The questionnaire was created by investigators of the project through a Delphi method, and was about service protocols concerning hemorrhagic patient care, hemorrhagic parameters measure equipment available, intravenous solutes and drugs as well as various medical devices useful or perceived to be useful to support prehospital hemorrhagic shock. The results are expressed in numbers and percentages. RESULTS: The overall response rate was 48% (n=178). Protocols were established in between 43% (n=76) and 47% (n=83) according to etiology, measuring devices were available in 5% (n=9) of the Smur for hemostasis up to 89% (n=158) for hemoglobin measurement. Available intravenous solutes were mainly isotonic salty serum (95%, n=169), hydroxylethylstarch (83%, n=148) and Ringer lactate (73%, n=130). Tranexamic acid was available in 84 (47%) Smur. The teams had access to erythrocytes concentrates, fresh frozen plasma and platelets in 84% (n=150), 44% (n=79) and 23% (n=41) respectively. Eighty-one (46%) Smur had tourniquets and 127 (71%) anti-shock trousers. Finally, 57 (32%) had a pelvic restraint belt. CONCLUSION: There is a great disparity in the means available in the French Smur for the support of prehospitalization bleeding. The majority the Smur physicians can transfuse in a prehospital setting. On the other hand, a minority of teams can actively warm patients, employ tranexamic acid or use pelvic restraint belts.

Accidental dural puncture: combination of prophylactic methods to avoid post-dural puncture headache.

Accidental dural puncture (ADP) is a common complication of epidural catheter insertion, and may lead to post-dural puncture headache (PDPH), especially in obstetric patients. Epidural blood patch (BP) is the most effective treatment of PDPH. Prophylactic BP has shown its efficacy to prevent PDPH; nevertheless, this method may be insufficient. We report an ADP case before induction of labor in a 28-year-old parturient. To avoid PDPH, an intrathecal catheter was immediately inserted after ADP and an epidural catheter was also inserted at the interspace above. Catheters were kept in place for more than 24hours. A prophylactic BP was performed immediately after removal of the intrathecal catheter. The patient did not experience any headache. This combination of treatments (intrathecal catheter insertion+prophylactic BP) may be a good alternative approach to prevent PDPH, even if it has to be warranted by other clinical studies.

Considerations for the Perioperative Care of Elderly and Frail Patients.

The number of elderly patients undergoing anesthesia is increasing. At the same time aging is associated with decreased functional reserve of all major organ systems and an increase in comorbid conditions, requiring a comprehensive perioperative evaluation to minimize morbidity and mortality. The preoperative assessment should focus on the risk/benefit analysis vis-à-vis the proposed intervention, allowing the practitioner to adapt surgical and anesthetic care, as well optimize health and functional status. In addition to the usual evaluation for cardiac and pulmonary risk, the preoperative assessment in the older patient should also address the risk of postoperative cognitive dysfunction and delirium. 'Do-not-resuscitate' orders must be clarified with the patients or substitute decision maker. Studies have not been able to clearly show the superiority of one anesthetic approach for the geriatric patient, although there are probably advantages to using regional anesthetic techniques. Overall the patient's preoperative functional status along with the proposed intervention is the primary determinants of the patient's long term functional outcome and wellbeing. The elderly patient may be at his most vulnerable during the postoperative phase, and a relatively high frequency of adverse events in the elderly, including respiratory insufficiency, myocardial and cerebrovascular ischemia, renal failure, infectious complications as well as delirium and postoperative cognitive dysfunction have been observed. Perioperative interventions should target modifiable risk factors and the avoidance of even minor complications with an ultimate goal of improving long-term outcome.

Study of agreement of aortic, radial and femoral blood pressures during aortic endografting.

PURPOSE: To estimate the agreement between radial or femoral, and ascending aortic invasive blood pressure values. PATIENTS AND METHODS: Prospective study on 32 patients who underwent an aortic endografting under general anesthesia. After deploying the prosthesis under controlled hypotension, a catheter was introduced in the aorta to measure the staged systolic (SAP), diastolic (DAP) and mean (MAP) arterial pressures, in particular at the level of ascending aorta and femoral artery. RESULTS: No differences were observed between SAP, DAP or MAP measured in the aorta versus femoral or radial arteries. A better agreement was observed between the aortic and femoral MAP (bias of 1mmHg, limits of agreement between: -8.8mmHg and +10.8mmHg) than between the aortic and the radial MAP (bias of 1.7mmHg, limits of agreement between: -14.1mmHg and +17.5mmHg). The comparison between radial and femoral MAP was not satisfying (bias of -4.7mmHg and limits of agreement between -19.1mmHg and +9.7mmHg). CONCLUSION: The femoral MAP is more accurate to predict value of the aortic MAP than the radial MAP in a hypotensive setting. The clinician should be aware of these discrepancies in conditions of hemodynamic impairment to optimize the treatment.

A prospective video-based observational and analytical approach to evaluate management during brain tumour surgery at a university hospital.

The operating room (OR) is a high-risk complex setting, where patient safety relies on the coordinated efforts of multiple team members. However, little attention has been paid to evaluating the strategies employed by OR practitioners to prevent and correct incidents that inevitably occur during surgery. Therefore, we were prompted to investigate human factor (HF) engineering methods that have been used in an innovative way in order to systematically observe and analyze the management of incidents in the neurosurgical OR of a French university hospital. A technical case report illustrates our approach that associates the following procedures: the recording of OR team member activities and behaviour by video cameras and direct observation of a HF researcher, with the description and the explicit demonstration of safety related procedures in self- and cross-confrontation interviews of OR team members. This technical report emphasizes complementary aspects of clinical performance related to safety skills. Moreover, individual and team performances rely on complementary abilities that associate practical knowledge, skills, and attitudes, which are engaged at various degrees to prevent and manage incidents. This report also enlightens new quality-improvement opportunities as well as further objectives for future studies.

[Video laryngoscopic tracheal intubation under sedation]. / Intubation au vidéolaryngoscope sous-sédation.

We report a video laryngoscopic tracheal intubation under sedation in a patient with a hip fracture. Preoperative assessment revealed signs of difficult airway management linked to a cervical spine immobilization. Here we describe an alternative method to awake fiber optic flexible intubation.

[Pulmonary embolism and pregnancy]. / Embolie pulmonaire et grossesse.

OBJECTIVE: Pulmonary embolism remains a leading cause of maternal death in France and in other developed countries. Prevention is well codified, but management remains complex both for diagnosis and therapeutics. The objective of this review was to update the knowledge on diagnosis and treatment of pulmonary embolism during pregnancy. ARTICLE TYPE: Review. DATA SOURCE: Medline(®) database looking for articles published in English or French between 1965 and 2012, using pulmonary embolism, pregnancy, heparin, thrombolysis and vena cava filter as keywords. Editorials, original articles, reviews and cases reports were selected. DATA SYNTHESIS: Pulmonary embolism is one of the leading causes of maternal death in France. Clinical signs and biologic tests are not specific during pregnancy. Doppler ultrasound is helpful for diagnosis and avoids maternal and fetal radiation. Treatment is based on full anticoagulation. Low molecular weight heparin is the treatment of choice. A temporary vena cava filter may be proposed, especially at the end of pregnancy, or when heparin is contraindicated. In case of pulmonary embolism with cardiogenic shock, thrombolysis is an alternative treatment. CONCLUSION: Diagnostic approach is first based on the use of ultrasound- Doppler, and frequently on-to computed tomographic pulmonary angiography or ventilation-perfusion lung scanning. The treatment is based on low molecular weight heparin. Others therapeutics, such as thrombolysis or temporary vena cava filter, may be useful in certain circumstances.

[Continuous spinal anesthesia and pulmonary arterial hypertension]. / Rachianesthésie continue et hypertension artérielle pulmonaire.

We report the use of continuous spinal anesthesia for hip fracture surgery in a patient with pulmonary arterial hypertension. Preoperative evaluation, anesthetic technique and preoperative monitoring are discussed.