Tacrolimus Monitoring in Liver Transplant Recipients, Posttransplant Cholestasis: A Comparative Between 2 Commercial Immunoassays and a Liquid Chromatography-Tandem Mass Spectrometry Method.

BACKGROUND: Cholestasis commonly occurs after orthotopic liver transplantation. It can be extrahepatic because of mechanical obstruction or intrahepatic because of various causes. During cholestasis episodes, blood concentrations of tacrolimus (TAC) metabolites may increase, potentially affecting TAC concentrations measured by immunoassays. This study aimed to simultaneously evaluate the analytical performance of 2 TAC immunoassays, a quantitative microsphere system (QMS) immunoassay, and chemiluminescence microparticle immunoassay, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) as a reference method in liver transplant recipients. METHODS: This single-center study included 265 patients who underwent orthotopic liver transplantation. In total, 942 blood samples were collected. TAC trough concentrations were measured using LC-MS/MS and 2 immunoassays in parallel. The plasma concentrations of conjugated bilirubin were measured in all samples. The results were analyzed using Bland-Altman plots and Passing-Bablok regressions. RESULTS: The Bland-Altman plot analysis showed that the TAC QMS immunoassay has a significant bias (+37%) compared with LC-MS/MS, and this bias was higher in patients with cholestasis with hyperbilirubinemia (≤+70% in patients with conjugated bilirubin >150 µmol/L). In comparison, the chemiluminescence microparticle immunoassay showed acceptable analytical performance in patients with hyperbilirubinemia (bias <10%). CONCLUSIONS: In agreement with previous findings, the TAC QMS immunoassay showed a positive bias compared with LC-MS/MS. This bias is remarkably high in patients with cholestasis and hyperbilirubinemia, suggesting the cross-reactivity of TAC metabolites with the monoclonal antibody used in the QMS immunoassay.

Nurse-to-Nurse Familiarity and Mortality in the Critically Ill: A Multicenter Observational Study.

Rationale: Nurse-to-nurse familiarity at work should strengthen the components of teamwork and enhance its efficiency. However, its impact on patient outcomes in critical care remains poorly investigated. Objectives: To explore the role of nurse-to-nurse familiarity on inpatient deaths during ICU stay. Methods: This was a retrospective observational study in eight adult academic ICUs between January 1, 2011 and December 31, 2016. Measurements and Main Results: Nurse-to-nurse familiarity was measured across day and night 12-hour daily shifts as the mean number of previous collaborations between each nursing team member during previous shifts within the given ICU (suboptimal if <50). Primary outcome was a shift with at least one inpatient death, excluding death of patients with a decision to forego life-sustaining therapy. A multiple modified Poisson regression was computed to identify the determinants of mortality per shift, taking into account ICU, patient characteristics, patient-to-nurse and patient-to-assistant nurse ratios, nurse experience length, and workload. A total of 43,479 patients were admitted, of whom 3,311 (8%) died. The adjusted model showed a lower risk of a shift with mortality when nurse-to-nurse familiarity increased in the shift (relative risk, 0.90; 95% confidence interval per 10 shifts, 0.82-0.98; P = 0.012). Low nurse-to-nurse familiarity during the shift combined with suboptimal patient-to-nurse and patient-to-assistant nurse ratios (suboptimal if >2.5 and >4, respectively) were associated with increased risk of shift with mortality (relative risk, 1.84; 95% confidence interval, 1.15-2.96; P < 0.001). Conclusions: Shifts with low nurse-to-nurse familiarity were associated with an increased risk of patient deaths.

Occurrences of post-traumatic stress disorder, anxiety, depression, and burnout syndrome in ICU staff workers after two-year of the COVID-19 pandemic: the international PSY-CO in ICU study.

PURPOSE: The present study aimed at assessing the prevalences of post-traumatic stress disorder (PTSD) (main objective), anxiety, depression, and burnout syndrome (BOS) and their associated factors in intensive care unit (ICU) staff workers in the second year of the COVID-19 pandemic. MATERIALS AND METHODS: An international cross-sectional multicenter ICU-based online survey was carried out among the ICU staff workers in 20 ICUs across 3 continents. ICUs staff workers (both caregivers and non-caregivers) were invited to complete PCL-5, HADS, and MBI questionnaires for assessing PTSD, anxiety, depression, and the different components of BOS, respectively. A personal questionnaire was used to isolate independent associated factors with these disorders. RESULTS: PCL-5, HADS, and MBI questionnaires were completed by 585, 570, and 539 responders, respectively (525 completed all questionnaires). PTSD was diagnosed in 98/585 responders (16.8%). Changing familial environment, being a non-caregiver staff worker, having not being involved in a COVID-19 patient admission, having not been provided with COVID-19-related information were associated with PTSD. Anxiety was reported in 130/570 responders (22.8%). Working in a public hospital, being a woman, being financially impacted, being a non-clinical healthcare staff member, having no theoretical or practical training on individual preventive measures, and fear of managing COVID-19 patients were associated with anxiety. Depression was reported in 50/570 responders (8.8%). Comorbidity at risk of severe COVID-19, working in a public hospital, looking after a child, being a non-caregiver staff member, having no information, and a request for moving from the unit were associated with depression. Having received no information and no adequate training for COVID-19 patient management were associated with all 3 dimensions of BOS. CONCLUSION: The present study confirmed that ICU staff workers, whether they treated COVID-19 patients or not, have a substantial prevalence of psychological disorders.

Extracorporeal Albumin Dialysis in Liver Failure with MARS and SPAD: A Randomized Crossover Trial.

INTRODUCTION: Liver failure is associated with hepatic and extrahepatic organ failure leading to a high short-term mortality rate. Extracorporeal albumin dialysis (ECAD) aims to reduce albumin-bound toxins accumulated during liver failure. ECAD detoxifies blood using albumin dialysis through an artificial semipermeable membrane with recirculation (molecular adsorbent recirculating system, MARS) or without (single-pass albumin dialysis, SPAD). METHODS: We performed a randomized crossover open trial in a surgical intensive care unit. The primary outcome of the study was total bilirubin reduction during MARS and during SPAD therapies. The secondary outcomes were conjugated bilirubin and bile acid level reduction during MARS and SPAD sessions and tolerance of dialysis system devices. Inclusion criteria were adult patients presenting liver failure with factor V activity <50% associated with bilirubin ≥250 µmol/L and a complication (either hepatic encephalopathy, severe pruritus, or hepatorenal syndrome). For MARS and SPAD, the dialysis flow rate was equal to 1,000 mL/h. RESULTS: Twenty crossovers have been performed. Baseline biochemical characteristics (bilirubin, ammonia, bile acids, creatinine, and urea) were not statistically different between MARS and SPAD. Both ECAD have led to a significant reduction in total bilirubin (-83 ± 67 µmol/L after MARS; -122 ± 118 µmol/L after SPAD session), conjugated bilirubin (-82 ± 61 µmol/L after MARS; -105 ± 96 µmol/L after SPAD session), and bile acid levels (-64 ± 75 µmol/L after MARS; -56 ± 56 µmol/L after SPAD session), all nondifferent comparing MARS to SPAD. CONCLUSION: A simple-to-perform SPAD therapy with equal to MARS dialysate flow parameters provides the same efficacy in bilirubin and bile acid removal. However, clinically relevant endpoints have to be evaluated in randomized trials to compare MARS and SPAD therapies and to define the place of SPAD in the liver failure care program.

Effect of intravenous lidocaine on pain after head and neck cancer surgery (ELICO trial): A randomised controlled trial.

BACKGROUND: Treatment of postoperative pain after ear, nose and throat (ENT) cancer surgery is mainly morphine administration. Additional systemic lidocaine has shown promising results in some surgical procedures. OBJECTIVE: The main objective was to evaluate morphine consumption in the first 48 postoperative hours after intra-operative lidocaine infusion during major ENT cancer surgery. DESIGN: A randomised, double-blind, placebo-controlled trial. SETTING: Bicentric study including a university hospital and a major cancer centre, conducted from December 2016 to December 2019. PATIENTS: A total of 144 patients undergoing major ENT cancer surgery were included. INTERVENTION: The patients were randomly assigned to receive intravenous lidocaine or placebo during surgery and in the recovery room. MAIN OUTCOME MEASURES: Endpoints were postoperative morphine consumption in the first 24 and 48 h postoperatively, intra-operative remifentanil consumption, adverse events occurrence and assessment 3 to 6 months after surgery with the McGill pain questionnaire. RESULTS: A total of 118 patients were included (lidocaine n  = 57; placebo n  = 61, 26 patients were excluded). There was no significant difference in morphine consumption during the first 48 postoperative hours in the lidocaine group compared with the placebo group with a median [IQR] of 0.60 [0.30 to 1.03] mg kg -1 vs. 0.57 [0.37 to 0.96] mg kg -1 , total dose 44 [21 to 73.3] mg vs. 38 [23.3 to 56.5] mg, P  = 0.92.There was no significant difference between the two groups in any of the other endpoints, including at follow up 3 to 6 months after surgery. CONCLUSION: Intravenous lidocaine in ENT cancer surgery did not show any additional analgesic or morphine-sparing effect 48 h after surgery. Three to six months after surgery, there was no significant difference in pain scores or consumption of analgesics. Patients treated pre-operatively with opioids were not evaluated in the study. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02894710 and EUDRACT number 2015-005799-90.

Prediction of intraoperative hypotension from the linear extrapolation of mean arterial pressure.

BACKGROUND: Hypotension prediction index (HPI) software is a proprietary machine learning-based algorithm used to predict intraoperative hypotension (IOH). HPI has shown superiority in predicting IOH when compared to the predictive value of changes in mean arterial pressure (ΔMAP) alone. However, the predictive value of ΔMAP alone, with no reference to the absolute level of MAP, is counterintuitive and poor at predicting IOH. A simple linear extrapolation of mean arterial pressure (LepMAP) is closer to the clinical approach. OBJECTIVES: Our primary objective was to investigate whether LepMAP better predicts IOH than ΔMAP alone. DESIGN: Retrospective diagnostic accuracy study. SETTING: Two tertiary University Hospitals between May 2019 and December 2019. PATIENTS: A total of 83 adult patients undergoing high risk non-cardiac surgery. DATA SOURCES: Arterial pressure data were automatically extracted from the anaesthesia data collection software (one value per minute). IOH was defined as MAP < 65 mmHg. ANALYSIS: Correlations for repeated measurements and the area under the curve (AUC) from receiver operating characteristics (ROC) were determined for the ability of LepMAP and ΔMAP to predict IOH at 1, 2 and 5 min before its occurrence (A-analysis, using the whole dataset). Data were also analysed after exclusion of MAP values between 65 and 75 mmHg (B-analysis). RESULTS: A total of 24 318 segments of ten minutes duration were analysed. In the A-analysis, ROC AUCs to predict IOH at 1, 2 and 5 min before its occurrence by LepMAP were 0.87 (95% confidence interval, CI, 0.86 to 0.88), 0.81 (95% CI, 0.79 to 0.83) and 0.69 (95% CI, 0.66 to 0.71) and for ΔMAP alone 0.59 (95% CI, 0.57 to 0.62), 0.61 (95% CI, 0.59 to 0.64), 0.57 (95% CI, 0.54 to 0.69), respectively. In the B analysis for LepMAP these were 0.97 (95% CI, 0.9 to 0.98), 0.93 (95% CI, 0.92 to 0.95) and 0.86 (95% CI, 0.84 to 0.88), respectively, and for ΔMAP alone 0.59 (95% CI, 0.53 to 0.58), 0.56 (95% CI, 0.54 to 0.59), 0.54 (95% CI, 0.51 to 0.57), respectively. LepMAP ROC AUCs were significantly higher than ΔMAP ROC AUCs in all cases. CONCLUSIONS: LepMAP provides reliable real-time and continuous prediction of IOH 1 and 2 min before its occurrence. LepMAP offers better discrimination than ΔMAP at 1, 2 and 5 min before its occurrence. Future studies evaluating machine learning algorithms to predict IOH should be compared with LepMAP rather than ΔMAP.

A retrospective comparison of COVID-19 and seasonal influenza mortality and outcomes in the ICUs of a French university hospital.

BACKGROUND: SARS-Cov-2 (COVID-19) has become a major worldwide health concern since its appearance in China at the end of 2019. OBJECTIVE: To evaluate the intrinsic mortality and burden of COVID-19 and seasonal influenza pneumonia in ICUs in the city of Lyon, France. DESIGN: A retrospective study. SETTING: Six ICUs in a single institution in Lyon, France. PATIENTS: Consecutive patients admitted to an ICU with SARS-CoV-2 pneumonia from 27 February to 4 April 2020 (COVID-19 group) and seasonal influenza pneumonia from 1 November 2015 to 30 April 2019 (influenza group). A total of 350 patients were included in the COVID-19 group (18 refused to consent) and 325 in the influenza group (one refused to consent). Diagnosis was confirmed by RT-PCR. Follow-up was completed on 1 April 2021. MAIN OUTCOMES AND MEASURES: Differences in 90-day adjusted-mortality between the COVID-19 and influenza groups were evaluated using a multivariable Cox proportional hazards model. RESULTS: COVID-19 patients were younger, mostly men and had a higher median BMI, and comorbidities, including immunosuppressive condition or respiratory history were less frequent. In univariate analysis, no significant differences were observed between the two groups regarding in-ICU mortality, 30, 60 and 90-day mortality. After Cox modelling adjusted on age, sex, BMI, cancer, sepsis-related organ failure assessment (SOFA) score, simplified acute physiology score SAPS II score, chronic obstructive pulmonary disease and myocardial infarction, the probability of death associated with COVID-19 was significantly higher in comparison to seasonal influenza [hazard ratio 1.57, 95% CI (1.14 to 2.17); P = 0.006]. The clinical course and morbidity profile of both groups was markedly different; COVID-19 patients had less severe illness at admission (SAPS II score, 37 [28 to 48] vs. 48 [39 to 61], P < 0.001 and SOFA score, 4 [2 to 8] vs. 8 [5 to 11], P < 0.001), but the disease was more severe considering ICU length of stay, duration of mechanical ventilation, PEEP level and prone positioning requirement. CONCLUSION: After ICU admission, COVID-19 was associated with an increased risk of death compared with seasonal influenza. Patient characteristics, clinical course and morbidity profile of these diseases is markedly different.

The use of a thromboelastometry-based algorithm reduces the need for blood product transfusion during orthotopic liver transplantation: A randomised controlled study.

BACKGROUND: Orthotopic liver transplantation is associated with a risk of bleeding. Coagulation in cirrhotic patients is difficult to assess with standard coagulation tests because of rebalanced coagulation. This can be better assessed by thromboelastometry which can detect coagulation impairments more specifically in such patients. OBJECTIVES: Our first objective was to compare the number of units of blood products transfused during liver transplantation when using an algorithm based on standard coagulation tests or a thromboelastometry-guided transfusion algorithm. DESIGN: Randomised controlled trial. SETTING: Single-centre tertiary care hospital in France, from December 2014 to August 2016. PARTICIPANTS: A total of 81 adult patients undergoing orthotopic liver transplantation were studied. Patients were excluded if they had congenital coagulopathies. INTERVENTION: Transfusion management during liver transplantation was guided either by a standard coagulation test algorithm or by a thromboelastometry-guided algorithm. Transfusion, treatments and postoperative outcomes were compared between groups. MAIN OUTCOME MEASURES: Total number of transfused blood product units during the operative period (1 U is one pack of red blood cells (RBCs), fresh frozen plasma (FFP) or platelets). RESULTS: Median [interquartile range] intra-operative transfusion requirement was reduced in the thromboelastometry group (3 [2 to 4] vs. 7 [4 to 10] U, P = 0.005). FFP and tranexamic acid were administered less frequently in the thromboelastometry group (respectively 15 vs. 46.3%, P = 0.002 and 27.5 vs. 58.5%, P = 0.005), whereas fibrinogen was more often infused in the thromboelastometry group (72.5 vs. 29.3%, P < 0.001). Median transfusions of FFP (3 [2 to 6] vs. 4 [2 to 7] U, P = 0.448), RBCs (3 [2 to 5] vs. 4 [2 to 6] U, P = 0.330) and platelets (1 [1 to 2] vs. 1 [1 to 2] U, P = 0.910) were not different between groups. In the postoperative period, RBC or platelet transfusion, the need for revision surgery or occurrence of haemorrhage were not different between groups. CONCLUSION: A transfusion algorithm based on thromboelastometry assessment of coagulation reduced the total number of blood product units transfused during liver transplantation, particularly FFP administration. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02352181.

Incidence and Risk Factors of Coagulation Profile Derangement After Liver Surgery: Implications for the Use of Epidural Analgesia-A Retrospective Cohort Study.

BACKGROUND: Hepatic surgery is a major abdominal surgery. Epidural analgesia may decrease the incidence of postoperative morbidities. Hemostatic disorders frequently occur after hepatic resection. Insertion or withdrawal (whether accidental or not) of an epidural catheter during coagulopathic state may cause an epidural hematoma. The aim of the study is to determine the incidence of coagulopathy after hepatectomy, interfering with epidural catheter removal, and to identify the risk factors related to coagulopathy. METHODS: We performed a retrospective review of a prospective, multicenter, observational database including patients over 18 years old with a history of liver resection. Main collected data were the following: age, preexisting cirrhosis, Child-Pugh class, preoperative and postoperative coagulation profiles, extent of liver resection, blood loss, blood products transfused during surgery. International normalized ratio (INR) ≥1.5 and/or platelet count <80,000/mm defined coagulopathy according to the neuraxial anesthesia guidelines. A logistic regression analysis was performed to assess the association between selected factors and a coagulopathic state after hepatic resection. RESULTS: One thousand three hundred seventy-one patients were assessed. Seven hundred fifty-nine patients had data available about postoperative coagulopathy, which was observed in 53.5% [95% confidence interval, 50.0-57.1]. Maximum derangement in INR occurred on the first postoperative day, and platelet count reached a trough peak on postoperative days 2 and 3. In the multivariable analysis, preexisting hepatic cirrhosis (odds ratio [OR] = 2.49 [1.38-4.51]; P = .003), preoperative INR ≥1.3 (OR = 2.39 [1.10-5.17]; P = .027), preoperative platelet count <150 G/L (OR = 3.03 [1.77-5.20]; P = .004), major hepatectomy (OR = 2.96 [2.07-4.23]; P < .001), and estimated intraoperative blood loss ≥1000 mL (OR = 1.85 [1.08-3.18]; P = .025) were associated with postoperative coagulopathy. CONCLUSIONS: Coagulopathy is frequent (53.5% [95% confidence interval, 50.0-57.1]) after liver resection. Epidural analgesia seems safe in patients undergoing minor hepatic resection without preexisting hepatic cirrhosis, showing a normal preoperative INR and platelet count.

Opioid-related genetic polymorphisms do not influence postoperative opioid requirement: A prospective observational study.

BACKGROUND: Among the various factors that may influence the pharmacological response to opioids, genetic polymorphisms [single nucleotide polymorphisms (SNP)] have generated some interest. OBJECTIVES: To examine the influence on morphine dose requirements and adverse events in the postoperative period of four SNP [opioid receptor mu1 (OPRM1), ATP-binding cassette subfamily B, member 1 (ABCB1) ex-21 and ex-26, catechol-o-methyltransferase (COMT)] in candidate genes involved in morphine pharmacodynamics and pharmacokinetics. DESIGN: A single centre prospective study. SETTING: University Hospital, Paris, France, from 2 January 2007 to 15 November 2011. PATIENTS: A total of 438 white adults scheduled for major orthopaedic surgery (spine, hip and knee) under general anaesthesia. The main exclusion criteria were receiving opioids for chronic pain, nonopioid drugs within 2 days prior to surgery, pregnancy, renal insufficiency, sleep apnoea obstruction syndrome, morbid obesity, severe hepatic impairment, cognitive dysfunction. INTERVENTIONS: Assays of plasma concentrations of morphine and metabolites (morphine 3-glucuronide and morphine 6-glucuronide) were performed and common polymorphisms in four candidate genes [OPRM1 A118G rs1799971; P-glycoprotein (ABCB1) T3435C (rs1045642) and G2677T/A (rs2032582); COMT Val 158 Met (rs4680)] were analysed.Morphine was titrated by staff in the postanaesthesia care unit (PACU) and in the ward patient-controlled intravenous analgesia was used for 24 h. MAIN OUTCOME MEASURES: The dose of morphine required to achieve pain relief and the influence of SNP in genes involved in morphine pharmacodynamics and kinetics on morphine dose requirements. Secondary endpoints were the concentrations of morphine, morphine 6-glucuronide and morphine 3-gluguronide, the proportion of patients requiring a rescue analgesic and the proportion of morphine-related adverse events. RESULTS: A total of 404 patients completed the study to final analysis. The mean ±â€ŠSD morphine dose to achieve pain relief was 15.8 ±â€Š8.8 mg in the PACU and 22.7 ±â€Š18.6 mg during patient-controlled intravenous administration. Morphine-related adverse events were observed in 37%. There was no relationship between any genetic polymorphisms and morphine dose, morphine 3-gluguronide and morphine 6-glucuronide concentration, morphine-related adverse events or pain level. In the PACU only, P-glycoprotein polymorphisms (ex-21; ex-26) were significantly associated with morphine concentration but the prediction of the model was poor (R = 0.04) CONCLUSION: No major relationship has been demonstrated between SNP of OPRM1, ABCB1, COMT and morphine requirement, pain level or adverse effects in the postoperative period. TRIAL REGISTRATION: NCT00822549 (www.clinicaltrials.gov).

Causes and Characteristics of Death in Intensive Care Units: A Prospective Multicenter Study.

BACKGROUND: Different modes of death are described in selected populations, but few data report the characteristics of death in a general intensive care unit population. This study analyzed the causes and characteristics of death of critically ill patients and compared anticipated death patients to unexpected death counterparts. METHODS: An observational multicenter cohort study was performed in 96 intensive care units. During 1 yr, each intensive care unit was randomized to participate during a 1-month period. Demographic data, characteristics of organ failures (Sequential Organ Failure Assessment subscore greater than or equal to 3), and organ supports were collected on all patients who died in the intensive care unit. Modes of death were defined as anticipated (after withdrawal or withholding of treatment or brain death) or unexpected (despite engagement of full-level care or sudden refractory cardiac arrest). RESULTS: A total of 698 patients were included during the study period. At the time of death, 84% had one or more organ failures (mainly hemodynamic) and 89% required at least one organ support (mainly mechanical ventilation). Deaths were considered unexpected and anticipated in 225 and 473 cases, respectively. Compared to its anticipated counterpart, unexpected death occurred earlier (1 day vs. 5 days; P< 0.001) and had fewer organ failures (1 [1 to 2] vs. 1 [1 to 3]; P< 0.01) and more organ supports (2 [2 to 3] vs. 1 [1 to 2]; P< 0.01). Withdrawal or withholding of treatments accounted for half of the deaths. CONCLUSIONS: In a general intensive care unit population, the majority of patients present with at least one organ failure at the time of death. Anticipated and unexpected deaths represent two different modes of dying and exhibit profiles reflecting the different pathophysiologic underlying mechanisms.

Early postoperative neuropathic pain assessed by the DN4 score predicts an increased risk of persistent postsurgical neuropathic pain.

BACKGROUND: Acute neuropathic pain can occur in the postoperative period but any link with persistent post-surgical neuropathic pain remains unclear. OBJECTIVES: The objectives of this study were to prospectively describe the incidence of acute post-surgical neuropathic pain in a large population using the DN4 (clinician administered) questionnaire and to confirm the hypothetical link between acute and persistent neuropathic pain at 2 months after surgery in a large population using the DN2 (self administered) questionnaire. DESIGN: A multi-centre, prospective and observational trial. SETTING: Two consecutive days in 27 hospitals in France. PATIENTS: Six hundred and eight patients undergoing 13 different types of surgery. Fifteen patients were excluded as data were incomplete, and 229 (38.6%) and 260 (43.8%) were not contactable for assessment at 1 and 2 months after surgery, respectively. MAIN OUTCOME MEASURES: Pain was evaluated at least 2 h postoperatively on the same day (D0),on the second day (D2) and at 1 and 2 months after surgery (M1 and M2). Pain was assessed using a 10-point Numeric Rating Scale. If the Numeric Rating Scale score was greater than 0, neuropathic pain was assessed using a DN4 (clinician administered) questionnaire or using a DN2 (self-administered) questionnaire. Acute and persistent postsurgical neuropathic pain (PPSNP) were defined respectively by a DN4 score at least 4/10 on day 0 and/or day 2 and a DN2 score at least 3/7 at 2 months after surgery. RESULTS: Of the 593 patients included, 41.2% were in pain before surgery and 8.2% described neuropathic pain. Early after surgery, the majority of the 593 patients (72.2% on the day of surgery and 71.3% on day 2) experienced acute pain. It was neuropathic in nature in 5.6% of patients (95% CI, 3.6 to 8.3) on the day of surgery and 12.9% (95% CI, 9.7 to 16.7) on day 2. Two months after surgery, PPSNP was present in 33.3% of the 333 patients assessed. Multivariate analysis showed that a DN4 score at least 4/10 on the day of surgery or on day 2 was a significant risk factor for PPSNP [odds ratios 4.22 (95% CI, 2.19 to 8.12)]. CONCLUSION: Our results suggest that early acute postsurgical neuropathic pain significantly increases the risk of persistent post-surgical neuropathic pain. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NTC NCT02826317.

Lack of Analgesic Effect Induced by Ropivacaine Wound Infiltration in Thyroid Surgery: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Surgical site infiltration with local anesthetic reduces analgesic requests in various types of surgeries. Because thyroid surgery may induce severe postoperative pain, we tested the hypothesis that ropivacaine surgical site infiltration would significantly decrease postoperative administration of morphine in patients undergoing thyroid surgery. METHODS: We performed a double-blind, placebo-controlled superiority trial to assess the efficacy of surgical site analgesia with ropivacaine (10 mL, 75 mg) performed at the end of thyroid surgery in adult patients. The primary end point was the proportion of patients not requiring IV morphine in the postanesthesia care unit. RESULTS: One hundred sixty-three patients completed the study, 85 in the placebo group and 88 in the ropivacaine group. The proportion of patients requiring morphine administration in the postanesthesia care unit (55% vs 53%, P = 0.80), the dose of IV morphine administered (5.6 ± 6.1 vs 5.5 ± 6.0 mg, P = 0.90), the total dose of opioids administered (expressed as oral morphine equivalent dose: 64 ± 27 vs 69 ± 29 mg, P = 0.20), and the visual analog pain scale over the first 24 hours were not significantly different between groups. The incidence of adverse events (36% vs 39%, P = 0.88), morphine-related adverse events (19% vs 17%, P = 0.84), serious adverse events (0% vs 2%, P = 0.50), and the patient satisfaction scores (9 ± 1 vs 9 ± 1, P = 0.70) was not significantly different between the 2 groups. CONCLUSIONS: Surgical site analgesia with ropivacaine at the end of thyroid surgery is not associated with any significant analgesic benefit.

Patient Mortality Is Associated With Staff Resources and Workload in the ICU: A Multicenter Observational Study.

OBJECTIVE: Matching healthcare staff resources to patient needs in the ICU is a key factor for quality of care. We aimed to assess the impact of the staffing-to-patient ratio and workload on ICU mortality. DESIGN: We performed a multicenter longitudinal study using routinely collected hospital data. SETTING: Information pertaining to every patient in eight ICUs from four university hospitals from January to December 2013 was analyzed. PATIENTS: A total of 5,718 inpatient stays were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We used a shift-by-shift varying measure of the patient-to-caregiver ratio in combination with workload to establish their relationships with ICU mortality over time, excluding patients with decision to forego life-sustaining therapy. Using a multilevel Poisson regression, we quantified ICU mortality-relative risk, adjusted for patient turnover, severity, and staffing levels. The risk of death was increased by 3.5 (95% CI, 1.3-9.1) when the patient-to-nurse ratio was greater than 2.5, and it was increased by 2.0 (95% CI, 1.3-3.2) when the patient-to-physician ratio exceeded 14. The highest ratios occurred more frequently during the weekend for nurse staffing and during the night for physicians (p < 0.001). High patient turnover (adjusted relative risk, 5.6 [2.0-15.0]) and the volume of life-sustaining procedures performed by staff (adjusted relative risk, 5.9 [4.3-7.9]) were also associated with increased mortality. CONCLUSIONS: This study proposes evidence-based thresholds for patient-to-caregiver ratios, above which patient safety may be endangered in the ICU. Real-time monitoring of staffing levels and workload is feasible for adjusting caregivers' resources to patients' needs.

Cefiderocol in Difficult-to-Treat Nf-GNB in ICU Settings.

BACKGROUND: The efficacy and safety of cefiderocol in ICU patients with difficult-to-treat resistance (DTR) non-fermenting Gram-negative bacteria (Nf-GNB) are not as well-established. Consequently, we conducted a cohort study to compare Cefiderocol with the Best Available Therapy (BAT) in ICU patients. METHODS: We included adult patients from 9 different ICUs, including a burn ICU unit, from 2019 to 2023 treated with Cefiderocol for DTR Nf-GNB isolated from the blood or lungs. We matched each patient at a 1:2 ratio based on the same DTR Nf-GBN isolated pathogen, and when possible, within the same type of ICU (burn unit or not). The primary endpoint of the study was the clinical cure at 15 days, with secondary endpoints including clinical cure at 30 days, relapse, and in-ICU mortality. For each outcome, adjusted odds ratios were estimated using bidirectional stepwise regression in a final model, which included 13 preselected confounders. RESULTS: We included 27 patients with cefiderocol, matched with 54 patients receiving the BAT. Four patients were not exactly matched on the type of ICU unit. Characteristics were comparable between groups, mostly male with a Charlson Comorbidity Index of 3 [1-5], and 28% had immunosuppression. Cefiderocol patients were most likely to have higher number of antibiotic lines. The main DTR Nf-GNB identified was Pseudomonas aeruginosa (81.5%), followed by Acinetobater baumanii (14.8%) and Stenotrophomonas maltophilia (3.7%). Pneumonia was the identified infection in 21 (78.8%) patients in the Cefiderocol group and in 51 (94.4%) patients in the BAT group (p = 0.054). Clinical cure at 15 and 30-day and the in-ICU mortality was comparable between groups, however relapse was higher in the cefiderocol group (8-29.6% vs. 4-7.4%;aOR 10.06[1.96;51.53]) CONCLUSION: Cefiderocol did not show an improvement in clinical cure or mortality rates compared to BAT in the treatment of DTR Nf-GNB, but it was associated with a higher relapse rate.

Comparison of mortality and outcomes of four respiratory viruses in the intensive care unit: a multicenter retrospective study.

This retrospective study aimed to compare the mortality and burden of respiratory syncytial virus (RSV group), SARS-CoV-2 (COVID-19 group), non-H1N1 (Seasonal influenza group) and H1N1 influenza (H1N1 group) in adult patients admitted to intensive care unit (ICU) with respiratory failure. A total of 807 patients were included. Mortality was compared between the four following groups: RSV, COVID-19, seasonal influenza, and H1N1 groups. Patients in the RSV group had significantly more comorbidities than the other patients. At admission, patients in the COVID-19 group were significantly less severe than the others according to the simplified acute physiology score-2 (SAPS-II) and sepsis-related organ failure assessment (SOFA) scores. Using competing risk regression, COVID-19 (sHR = 1.61; 95% CI 1.10; 2.36) and H1N1 (sHR = 1.87; 95% CI 1.20; 2.93) were associated with a statistically significant higher mortality while seasonal influenza was not (sHR = 0.93; 95% CI 0.65; 1.31), when compared to RSV. Despite occurring in more severe patients, RSV and seasonal influenza group appear to be associated with a more favorable outcome than COVID-19 and H1N1 groups.