Intraoperative individualization of positive-end-expiratory pressure through electrical impedance tomography or esophageal pressure assessment: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: This systematic review of randomized-controlled trials (RCTs) with meta-analyses aimed to compare the effects on intraoperative arterial oxygen tension to inspired oxygen fraction ratio (PaO2/FiO2), exerted by positive end-expiratory pressure (PEEP) individualized trough electrical impedance tomography (EIT) or esophageal pressure (Pes) assessment (intervention) vs. PEEP not tailored on EIT or Pes (control), in patients undergoing abdominal or pelvic surgery with an open or laparoscopic/robotic approach. METHODS: PUBMED®, EMBASE®, and Cochrane Controlled Clinical trials register were searched for observational studies and RCTs from inception to the end of August 2022. Inclusion criteria were: RCTs comparing PEEP titrated on EIT/Pes assessment vs. PEEP not individualized on EIT/Pes and reporting intraoperative PaO2/FiO2. Two authors independently extracted data from the enrolled investigations. Data are reported as mean difference and 95% confidence interval (CI). RESULTS: Six RCTs were included for a total of 240 patients undergoing general anesthesia for surgery, of whom 117 subjects in the intervention group and 123 subjects in the control group. The intraoperative mean PaO2/FiO2 was 69.6 (95%CI 32.-106.4 ) mmHg higher in the intervention group as compared with the control group with 81.4% between-study heterogeneity (p < 0.01). However, at meta-regression, the between-study heterogeneity diminished to 44.96% when data were moderated for body mass index (estimate 3.45, 95%CI 0.78-6.11, p = 0.011). CONCLUSIONS: In patients undergoing abdominal or pelvic surgery with an open or laparoscopic/robotic approach, PEEP personalized by EIT or Pes allowed the achievement of a better intraoperative oxygenation compared to PEEP not individualized through EIT or Pes. PROSPERO REGISTRATION NUMBER: CRD 42021218306, 30/01/2023.

Evaluating prediction methods for glomerular filtration to optimise drug doses in obese and nonobese patients.

AIMS: The most suitable method for predicting the glomerular filtration rate (GFR) in obesity is currently debated. Therefore, multiple GFR/creatinine clearance prediction methods were applied to (morbidly) obese and nonobese patients ranging from moderate renal impairment to glomerular hyperfiltration and their predictions were rated based on observed fosfomycin pharmacokinetics, as this model drug is exclusively eliminated via glomerular filtration. METHODS: The GFR/creatinine clearance predictions via the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Modification of Diet in Renal Disease (MDRD; indexed and de-indexed by body surface area) and creatinine clearance via the Cockcroft-Gault formula (CLCRCG ) using different body size descriptors were compared to the fosfomycin clearance (CLFOF ) from 30 surgical patients (body mass index = 20.1-52.0 kg m-2 ), receiving 8000 mg as intravenous infusion. RESULTS: The concordance between CLFOF and creatinine clearance predictions was highest for CLCRCG employing either ideal body weight or adjusted body weight (if body mass >1.3 ideal body weight; CLCRCG_ABW-Schwartz , concordance-correlation coefficient [95% confidence interval] = 0.474 [0.156; 0.703], CCC) and GFR predictions via the de-indexed MDRD equation (concordance-correlation coefficient = 0.452 [0.137; 0.685]). The proportion of predicted GFR values within ±30% of the observed CLFOF (P30 = 72.3-76.7%) was only marginally lower than the reported P30 in the original CKD-EPI and MDRD publications (P30 = 84.1-90.0%). CONCLUSION: This analysis represents a successful proof-of-concept for evaluating GFR/creatinine clearance prediction methods: Across all body mass index classes CLCRCG_ABW-Schwartz or the de-indexed MDRD were most suitable for predicting creatinine clearance/GFR also in (morbidly) obese, CKD stage <3B individuals in therapeutic use. Their application is proposed in optimising doses for vital therapies in obese patients requiring monitoring of renal function (e.g. methotrexate dosing).

Inhibition of Caspase-1 with Tetracycline Ameliorates Acute Lung Injury.

Rationale: Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome with a mortality of up to 40%. Precision medicine approaches targeting patients on the basis of their molecular phenotypes of ARDS might help to identify effective pharmacotherapies. The inflammasome-caspase-1 pathway contributes to the development of ARDS via IL-1ß and IL-18 production. Recent studies indicate that tetracycline can be used to treat inflammatory diseases mediated by IL-1ß and IL-18, although the molecular mechanism by which tetracycline inhibits inflammasome-caspase-1 signaling remains unknown. Objectives: To identify patients with ARDS characterized by IL-1ß and IL-18 expression and investigate the ability of tetracycline to inhibit inflammasome-caspase-1 signaling in ARDS. Methods: IL-1ß and IL-18 concentrations were quantified in BAL fluid from patients with ARDS. Tetracycline's effects on lung injury and inflammation were assessed in two mouse models of direct (pulmonary) acute lung injury, and its effects on IL-1ß and IL-18 production were assessed by alveolar leukocytes from patients with direct ARDS ex vivo. Murine macrophages were used to further characterize the effect of tetracycline on the inflammasome-caspase-1 pathway. Measurements and Main Results: BAL fluid concentrations of IL-1ß and IL-18 are significantly higher in patients with direct ARDS than those with indirect (nonpulmonary) ARDS. In experimental acute lung injury, tetracycline significantly diminished lung injury and pulmonary inflammation by selectively inhibiting caspase-1-dependent IL-1ß and IL-18 production, leading to improved survival. Tetracycline also reduced the production of IL-1ß and IL-18 by alveolar leukocytes from patients with direct ARDS. Conclusions: Tetracycline may be effective in the treatment of direct ARDS in patients with elevated caspase-1 activity. Clinical Trial registered with www.clinicaltrials.gov (NCT04079426).

Geo-economic variations in epidemiology, ventilation management and outcome of patients receiving intraoperative ventilation during general anesthesia- posthoc analysis of an observational study in 29 countries.

BACKGROUND: The aim of this analysis is to determine geo-economic variations in epidemiology, ventilator settings and outcome in patients receiving general anesthesia for surgery. METHODS: Posthoc analysis of a worldwide study in 29 countries. Lower and upper middle-income countries (LMIC and UMIC), and high-income countries (HIC) were compared. The coprimary endpoint was the risk for and incidence of postoperative pulmonary complications (PPC); secondary endpoints were intraoperative ventilator settings, intraoperative complications, hospital stay and mortality. RESULTS: Of 9864 patients, 4% originated from LMIC, 11% from UMIC and 85% from HIC. The ARISCAT score was 17.5 [15.0-26.0] in LMIC, 16.0 [3.0-27.0] in UMIC and 15.0 [3.0-26.0] in HIC (P = .003). The incidence of PPC was 9.0% in LMIC, 3.2% in UMIC and 2.5% in HIC (P < .001). Median tidal volume in ml kg- 1 predicted bodyweight (PBW) was 8.6 [7.7-9.7] in LMIC, 8.4 [7.6-9.5] in UMIC and 8.1 [7.2-9.1] in HIC (P < .001). Median positive end-expiratory pressure in cmH2O was 3.3 [2.0-5.0]) in LMIC, 4.0 [3.0-5.0] in UMIC and 5.0 [3.0-5.0] in HIC (P < .001). Median driving pressure in cmH2O was 14.0 [11.5-18.0] in LMIC, 13.5 [11.0-16.0] in UMIC and 12.0 [10.0-15.0] in HIC (P < .001). Median fraction of inspired oxygen in % was 75 [50-80] in LMIC, 50 [50-63] in UMIC and 53 [45-70] in HIC (P < .001). Intraoperative complications occurred in 25.9% in LMIC, in 18.7% in UMIC and in 37.1% in HIC (P < .001). Hospital mortality was 0.0% in LMIC, 1.3% in UMIC and 0.6% in HIC (P = .009). CONCLUSION: The risk for and incidence of PPC is higher in LMIC than in UMIC and HIC. Ventilation management could be improved in LMIC and UMIC. TRIAL REGISTRATION: Clinicaltrials.gov , identifier: NCT01601223.

Distribution of ventilation and oxygenation in surgical obese patients ventilated with high versus low positive end-expiratory pressure: A substudy of a randomised controlled trial.

BACKGROUND: Intra-operative ventilation using low/physiological tidal volume and positive end-expiratory pressure (PEEP) with periodic alveolar recruitment manoeuvres (ARMs) is recommended in obese surgery patients. OBJECTIVES: To investigate the effects of PEEP levels and ARMs on ventilation distribution, oxygenation, haemodynamic parameters and cerebral oximetry. DESIGN: A substudy of a randomised controlled trial. SETTING: Tertiary medical centre in Geneva, Switzerland, between 2015 and 2018. PATIENTS: One hundred and sixty-two patients with a BMI at least 35 kg per square metre undergoing elective open or laparoscopic surgery lasting at least 120 min. INTERVENTION: Patients were randomised to PEEP of 4 cmH 2 O ( n  = 79) or PEEP of 12 cmH 2 O with hourly ARMs ( n  = 83). MAIN OUTCOME MEASURES: The primary endpoint was the fraction of ventilation in the dependent lung as measured by electrical impedance tomography. Secondary endpoints were the oxygen saturation index (SaO 2 /FIO 2 ratio), respiratory and haemodynamic parameters, and cerebral tissue oximetry. RESULTS: Compared with low PEEP, high PEEP was associated with smaller intra-operative decreases in dependent lung ventilation [-11.2%; 95% confidence interval (CI) -8.7 to -13.7 vs. -13.9%; 95% CI -11.7 to -16.5; P  = 0.029], oxygen saturation index (-49.6%; 95% CI -48.0 to -51.3 vs. -51.3%; 95% CI -49.6 to -53.1; P  < 0.001) and a lower driving pressure (-6.3 cmH 2 O; 95% CI -5.7 to -7.0). Haemodynamic parameters did not differ between the groups, except at the end of ARMs when arterial pressure and cardiac index decreased on average by -13.7 mmHg (95% CI -12.5 to -14.9) and by -0.54 l min -1  m -2 (95% CI -0.49 to -0.59) along with increased cerebral tissue oximetry (3.0 and 3.2% on left and right front brain, respectively). CONCLUSION: In obese patients undergoing abdominal surgery, intra-operative PEEP of 12 cmH 2 O with periodic ARMs, compared with intra-operative PEEP of 4 cmH 2 O without ARMs, slightly redistributed ventilation to dependent lung zones with minor improvements in peripheral and cerebral oxygenation. TRIAL REGISTRATION: NCT02148692, https://clinicaltrials.gov/ct2.

Outcome of acute hypoxaemic respiratory failure: insights from the LUNG SAFE Study.

BACKGROUND: Current incidence and outcome of patients with acute hypoxaemic respiratory failure requiring mechanical ventilation in the intensive care unit (ICU) are unknown, especially for patients not meeting criteria for acute respiratory distress syndrome (ARDS). METHODS: An international, multicentre, prospective cohort study of patients presenting with hypoxaemia early in the course of mechanical ventilation, conducted during four consecutive weeks in the winter of 2014 in 459 ICUs from 50 countries (LUNG SAFE). Patients were enrolled with arterial oxygen tension/inspiratory oxygen fraction ratio ≤300 mmHg, new pulmonary infiltrates and need for mechanical ventilation with a positive end-expiratory pressure of ≥5 cmH2O. ICU prevalence, causes of hypoxaemia, hospital survival and factors associated with hospital mortality were measured. Patients with unilateral versus bilateral opacities were compared. FINDINGS: 12 906 critically ill patients received mechanical ventilation and 34.9% with hypoxaemia and new infiltrates were enrolled, separated into ARDS (69.0%), unilateral infiltrate (22.7%) and congestive heart failure (CHF; 8.2%). The global hospital mortality was 38.6%. CHF patients had a mortality comparable to ARDS (44.1% versus 40.4%). Patients with unilateral-infiltrate had lower unadjusted mortality, but similar adjusted mortality compared to those with ARDS. The number of quadrants on chest imaging was associated with an increased risk of death. There was no difference in mortality comparing patients with unilateral-infiltrate and ARDS with only two quadrants involved. INTERPRETATION: More than one-third of patients receiving mechanical ventilation have hypoxaemia and new infiltrates with a hospital mortality of 38.6%. Survival is dependent on the degree of pulmonary involvement whether or not ARDS criteria are reached.

Perioperative administration of cefazolin and metronidazole in obese and non-obese patients: a pharmacokinetic study in plasma and interstitial fluid.

OBJECTIVES: To assess plasma and tissue pharmacokinetics of cefazolin and metronidazole in obese patients undergoing bariatric surgery and non-obese patients undergoing intra-abdominal surgery. PATIENTS AND METHODS: Fifteen obese and 15 non-obese patients received an IV short infusion of 2 g cefazolin and 0.5 g metronidazole for perioperative prophylaxis. Plasma and microdialysate from subcutaneous tissue were sampled until 8 h after dosing. Drug concentrations were determined by HPLC-UV. Pharmacokinetic parameters were calculated non-compartmentally. RESULTS: In obese patients (BMI 39.5-69.3 kg/m2) compared with non-obese patients (BMI 18.7-29.8 kg/m2), mean Cmax of total cefazolin in plasma was lower (115 versus 174 mg/L) and Vss was higher (19.4 versus 14.2 L). The mean differences in t½ (2.7 versus 2.4 h), CL (5.14 versus 4.63 L/h) and AUC∞ (402 versus 450 mg·h/L) were not significant. The influence of obesity on the pharmacokinetics of metronidazole was similar (Cmax 8.99 versus 14.7 mg/L, Vss 73.9 versus 51.8 L, t½ 11.9 versus 9.1 h, CL 4.62 versus 4.13 L/h, AUC∞ 116 versus 127 mg·h/L). Regarding interstitial fluid (ISF), mean concentrations of cefazolin remained >4 mg/L until 6 h in both groups, and those of metronidazole up to 8 h in the non-obese group. In obese patients, the mean ISF concentrations of metronidazole were between 3 and 3.5 mg/L throughout the measuring interval. CONCLUSIONS: During the time of surgery, cefazolin concentrations in plasma and ISF of subcutaneous tissue were lower in obese patients, but not clinically relevant. Regarding metronidazole, the respective differences were higher, and may influence dosing of metronidazole for perioperative prophylaxis in obese patients.

Individualized versus Fixed Positive End-expiratory Pressure for Intraoperative Mechanical Ventilation in Obese Patients: A Secondary Analysis.

BACKGROUND: General anesthesia may cause atelectasis and deterioration in oxygenation in obese patients. The authors hypothesized that individualized positive end-expiratory pressure (PEEP) improves intraoperative oxygenation and ventilation distribution compared to fixed PEEP. METHODS: This secondary analysis included all obese patients recruited at University Hospital of Leipzig from the multicenter Protective Intraoperative Ventilation with Higher versus Lower Levels of Positive End-Expiratory Pressure in Obese Patients (PROBESE) trial (n = 42) and likewise all obese patients from a local single-center trial (n = 54). Inclusion criteria for both trials were elective laparoscopic abdominal surgery, body mass index greater than or equal to 35 kg/m2, and Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) score greater than or equal to 26. Patients were randomized to PEEP of 4 cm H2O (n = 19) or a recruitment maneuver followed by PEEP of 12 cm H2O (n = 21) in the PROBESE study. In the single-center study, they were randomized to PEEP of 5 cm H2O (n = 25) or a recruitment maneuver followed by individualized PEEP (n = 25) determined by electrical impedance tomography. Primary endpoint was Pao2/inspiratory oxygen fraction before extubation and secondary endpoints included intraoperative tidal volume distribution to dependent lung and driving pressure. RESULTS: Ninety patients were evaluated in three groups after combining the two lower PEEP groups. Median individualized PEEP was 18 (interquartile range, 16 to 22; range, 10 to 26) cm H2O. Pao2/inspiratory oxygen fraction before extubation was 515 (individual PEEP), 370 (fixed PEEP of 12 cm H2O), and 305 (fixed PEEP of 4 to 5 cm H2O) mmHg (difference to individualized PEEP, 145; 95% CI, 91 to 200; P < 0.001 for fixed PEEP of 12 cm H2O and 210; 95% CI, 164 to 257; P < 0.001 for fixed PEEP of 4 to 5 cm H2O). Intraoperative tidal volume in the dependent lung areas was 43.9% (individualized PEEP), 25.9% (fixed PEEP of 12 cm H2O) and 26.8% (fixed PEEP of 4 to 5 cm H2O) (difference to individualized PEEP: 18.0%; 95% CI, 8.0 to 20.7; P < 0.001 for fixed PEEP of 12 cm H2O and 17.1%; 95% CI, 10.0 to 20.6; P < 0.001 for fixed PEEP of 4 to 5 cm H2O). Mean intraoperative driving pressure was 9.8 cm H2O (individualized PEEP), 14.4 cm H2O (fixed PEEP of 12 cm H2O), and 18.8 cm H2O (fixed PEEP of 4 to 5 cm H2O), P < 0.001. CONCLUSIONS: This secondary analysis of obese patients undergoing laparoscopic surgery found better oxygenation, lower driving pressures, and redistribution of ventilation toward dependent lung areas measured by electrical impedance tomography using individualized PEEP. The impact on patient outcome remains unclear.

The Association of Intraoperative driving pressure with postoperative pulmonary complications in open versus closed abdominal surgery patients - a posthoc propensity score-weighted cohort analysis of the LAS VEGAS study.

BACKGROUND: It is uncertain whether the association of the intraoperative driving pressure (ΔP) with postoperative pulmonary complications (PPCs) depends on the surgical approach during abdominal surgery. Our primary objective was to determine and compare the association of time-weighted average ΔP (ΔPTW) with PPCs. We also tested the association of ΔPTW with intraoperative adverse events. METHODS: Posthoc retrospective propensity score-weighted cohort analysis of patients undergoing open or closed abdominal surgery in the 'Local ASsessment of Ventilatory management during General Anaesthesia for Surgery' (LAS VEGAS) study, that included patients in 146 hospitals across 29 countries. The primary endpoint was a composite of PPCs. The secondary endpoint was a composite of intraoperative adverse events. RESULTS: The analysis included 1128 and 906 patients undergoing open or closed abdominal surgery, respectively. The PPC rate was 5%. ΔP was lower in open abdominal surgery patients, but ΔPTW was not different between groups. The association of ΔPTW with PPCs was significant in both groups and had a higher risk ratio in closed compared to open abdominal surgery patients (1.11 [95%CI 1.10 to 1.20], P <  0.001 versus 1.05 [95%CI 1.05 to 1.05], P <  0.001; risk difference 0.05 [95%CI 0.04 to 0.06], P <  0.001). The association of ΔPTW with intraoperative adverse events was also significant in both groups but had higher odds ratio in closed compared to open abdominal surgery patients (1.13 [95%CI 1.12- to 1.14], P <  0.001 versus 1.07 [95%CI 1.05 to 1.10], P <  0.001; risk difference 0.05 [95%CI 0.030.07], P <  0.001). CONCLUSIONS: ΔP is associated with PPC and intraoperative adverse events in abdominal surgery, both in open and closed abdominal surgery. TRIAL REGISTRATION: LAS VEGAS was registered at clinicaltrials.gov (trial identifier NCT01601223 ).

Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study.

BACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients. OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference. DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries. MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation. RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P < 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT. CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV. TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223.

The effects of preoperative moderate to severe anaemia on length of hospital stay: A propensity score-matched analysis in non-cardiac surgery patients.

BACKGROUND: Anaemia is frequently recorded during preoperative screening and has been suggested to affect outcomes after surgery negatively. OBJECTIVES: The objectives were to assess the frequency of moderate to severe anaemia and its association with length of hospital stay. DESIGN: Post hoc analysis of the international observational prospective 'Local ASsessment of VEntilatory management during General Anaesthesia for Surgery' (LAS VEGAS) study. PATIENTS AND SETTING: The current analysis included adult patients requiring general anaesthesia for non-cardiac surgery. Preoperative anaemia was defined as a haemoglobin concentration of 11 g dl-1 or lower, thus including moderate and severe anaemia according to World Health Organisation criteria. MAIN OUTCOME MEASURES: The primary outcome was length of hospital stay. Secondary outcomes included hospital mortality, intra-operative adverse events and postoperative pulmonary complications (PPCs). RESULTS: Haemoglobin concentrations were available for 8264 of 9864 patients. Preoperative moderate to severe anaemia was present in 7.7% of patients. Multivariable analysis showed that preoperative moderate to severe anaemia was associated with an increased length of hospital stay with a mean difference of 1.3 ((95% CI 0.8 to 1.8) days; P < .001). In the propensity-matched analysis, this association remained present, median 4.0 [IQR 1.0 to 5.0] vs. 2.0 [IQR 0.0 to 5.0] days, P = .001. Multivariable analysis showed an increased in-hospital mortality (OR 2.9 (95% CI 1.1 to 7.5); P  = .029), and higher incidences of intra-operative hypotension (36.3 vs. 25.3%; P < .001) and PPCs (17.1 vs. 10.5%; P = .001) in moderately to severely anaemic patients. However, this was not confirmed in the propensity score-matched analysis. CONCLUSIONS: In this international cohort of non-cardiac surgical patients, preoperative moderate to severe anaemia was associated with a longer duration of hospital stay but not increased intra-operative complications, PPCs or in-hospital mortality. TRIAL REGISTRATION: The LAS VEGAS study was registered at Clinicaltrials.gov, NCT01601223.

[Intraoperative Ventilation in Adults]. / Intraoperative Beatmung bei Erwachsenen.

Avoiding postoperative pulmonary complications (PPC) is an important goal for anesthesiologists during general anesthesia, and ventilation strategies may play a role. It seems reasonable to apply knowledge from lessons we learned from ventilation of intensive care unit patients aiming at avoiding ventilator associated lung injury. Ventilation associated lung injuries occur frequently and are associated with substantial morbidity and mortality. Strategies of lung protective ventilation, like lower tidal volumes and the use of positive end-expiatory pressure (PEEP), can usually be transferred safely to perioperative ventilation, although some issues such as hemodynamic side effects must be considered. For some reasons, however, current evidence is conflicting and there is no consensus on ventilatory perioperative management to avoid PPCs so far. This paper briefly summarizes physiological backgrounds in a functional context, current evidence, and provides some recommendations at "expert" opinion level for perioperative ventilation procedures.Especially in patients at risk and/or during surgery with higher surgical trauma and inflammation, we recommend limiting tidal volume to 6 - 8 ml/kg predicted body weight and the use of PEEP, which should be individualized e.g. by minimizing driving pressure. Recruitment maneuvers may be considered and should be carried out by using the ventilator.Obese patients are an increasing entity and can be challenging during anesthesia and ventilation. From a physiological point of view, these patients require much higher ventilation pressures as currently used, although recent evidence is not in favor of using moderately higher PEEP, which is matter of discussion.

Individualized Positive End-expiratory Pressure and Regional Gas Exchange in Porcine Lung Injury.

BACKGROUND: In acute respiratory failure elevated intraabdominal pressure aggravates lung collapse, tidal recruitment, and ventilation inhomogeneity. Low positive end-expiratory pressure (PEEP) may promote lung collapse and intrapulmonary shunting, whereas high PEEP may increase dead space by inspiratory overdistension. The authors hypothesized that an electrical impedance tomography-guided PEEP approach minimizing tidal recruitment improves regional ventilation and perfusion matching when compared to a table-based low PEEP/no recruitment and an oxygenation-guided high PEEP/full recruitment strategy in a hybrid model of lung injury and elevated intraabdominal pressure. METHODS: In 15 pigs with oleic acid-induced lung injury intraabdominal pressure was increased by intraabdominal saline infusion. PEEP was set in randomized order: (1) guided by a PEEP/inspired oxygen fraction table, without recruitment maneuver; (2) minimizing tidal recruitment guided by electrical impedance tomography after a recruitment maneuver; and (3) maximizing oxygenation after a recruitment maneuver. Single photon emission computed tomography was used to analyze regional ventilation, perfusion, and aeration. Primary outcome measures were differences in PEEP levels and regional ventilation/perfusion matching. RESULTS: Resulting PEEP levels were different (mean ± SD) with (1) table PEEP: 11 ± 3 cm H2O; (2) minimal tidal recruitment PEEP: 22 ± 3 cm H2O; and (3) maximal oxygenation PEEP: 25 ± 4 cm H2O; P < 0.001. Table PEEP without recruitment maneuver caused highest lung collapse (28 ± 11% vs. 5 ± 5% vs. 4 ± 4%; P < 0.001), shunt perfusion (3.2 ± 0.8 l/min vs. 1.0 ± 0.8 l/min vs. 0.7 ± 0.6 l/min; P < 0.001) and dead space ventilation (2.9 ± 1.0 l/min vs. 1.5 ± 0.7 l/min vs. 1.7 ± 0.8 l/min; P < 0.001). Although resulting in different PEEP levels, minimal tidal recruitment and maximal oxygenation PEEP, both following a recruitment maneuver, had similar effects on regional ventilation/perfusion matching. CONCLUSIONS: When compared to table PEEP without a recruitment maneuver, both minimal tidal recruitment PEEP and maximal oxygenation PEEP following a recruitment maneuver decreased shunting and dead space ventilation, and the effects of minimal tidal recruitment PEEP and maximal oxygenation PEEP were comparable.

Individualised positive end-expiratory pressure guided by electrical impedance tomography for robot-assisted laparoscopic radical prostatectomy: a prospective, randomised controlled clinical trial.

BACKGROUND: Robot-assisted laparoscopic radical prostatectomy requires general anaesthesia, extreme Trendelenburg positioning and capnoperitoneum. Together these promote impaired pulmonary gas exchange caused by atelectasis and may contribute to postoperative pulmonary complications. In morbidly obese patients, a recruitment manoeuvre (RM) followed by individualised PEEP improves intraoperative oxygenation and end-expiratory lung volume (EELV). We hypothesised that individualised PEEP with initial RM similarly improves intraoperative oxygenation and EELV in non-obese individuals undergoing robot-assisted prostatectomy. METHODS: Forty males (age, 49-76 yr; BMI <30 kg m-2) undergoing prostatectomy received volume-controlled ventilation (tidal volume 8 ml kg-1 predicted body weight). Participants were randomised to either (1) RM followed by individualised PEEP (RM/PEEPIND) optimised using electrical impedance tomography or (2) no RM with 5 cm H2O PEEP. The primary outcome was the ratio of arterial oxygen partial pressure to fractional inspired oxygen (Pao2/Fio2) before the last RM before extubation. Secondary outcomes included regional ventilation distribution and EELV which were measured before, during, and after anaesthesia. The cardiovascular effects of RM/PEEPIND were also assessed. RESULTS: In 20 males randomised to RM/PEEPIND, the median PEEPIND was 14 cm H2O [inter-quartile range, 8-20]. The Pao2/Fio2 was 10.0 kPa higher with RM/PEEPIND before extubation (95% confidence interval [CI], 2.6-17.3 kPa; P=0.001). RM/PEEPIND increased end-expiratory lung volume by 1.49 L (95% CI, 1.09-1.89 L; P<0.001). RM/PEEPIND also improved the regional ventilation of dependent lung regions. Vasopressor and fluid therapy was similar between groups, although 13 patients randomised to RM/PEEPIND required pharmacological therapy for bradycardia. CONCLUSION: In non-obese males, an individualised ventilation strategy improved intraoperative oxygenation, which was associated with higher end-expiratory lung volumes during robot-assisted laparoscopic prostatectomy. CLINICAL TRIAL REGISTRATION: DRKS00004199 (German clinical trials registry).

Intraoperative ventilator settings and their association with postoperative pulmonary complications in neurosurgical patients: post-hoc analysis of LAS VEGAS study.

BACKGROUND: Limited information is available regarding intraoperative ventilator settings and the incidence of postoperative pulmonary complications (PPCs) in patients undergoing neurosurgical procedures. The aim of this post-hoc analysis of the 'Multicentre Local ASsessment of VEntilatory management during General Anaesthesia for Surgery' (LAS VEGAS) study was to examine the ventilator settings of patients undergoing neurosurgical procedures, and to explore the association between perioperative variables and the development of PPCs in neurosurgical patients. METHODS: Post-hoc analysis of LAS VEGAS study, restricted to patients undergoing neurosurgery. Patients were stratified into groups based on the type of surgery (brain and spine), the occurrence of PPCs and the assess respiratory risk in surgical patients in Catalonia (ARISCAT) score risk for PPCs. RESULTS: Seven hundred eighty-four patients were included in the analysis; 408 patients (52%) underwent spine surgery and 376 patients (48%) brain surgery. Median tidal volume (VT) was 8 ml [Interquartile Range, IQR = 7.3-9] per predicted body weight; median positive end-expiratory pressure (PEEP) was 5 [3 to 5] cmH20. Planned recruitment manoeuvres were used in the 6.9% of patients. No differences in ventilator settings were found among the sub-groups. PPCs occurred in 81 patients (10.3%). Duration of anaesthesia (odds ratio, 1.295 [95% confidence interval 1.067 to 1.572]; p = 0.009) and higher age for the brain group (odds ratio, 0.000 [0.000 to 0.189]; p = 0.031), but not intraoperative ventilator settings were independently associated with development of PPCs. CONCLUSIONS: Neurosurgical patients are ventilated with low VT and low PEEP, while recruitment manoeuvres are seldom applied. Intraoperative ventilator settings are not associated with PPCs.

Spontaneous Breathing in Early Acute Respiratory Distress Syndrome: Insights From the Large Observational Study to UNderstand the Global Impact of Severe Acute Respiratory FailurE Study.

OBJECTIVES: To describe the characteristics and outcomes of patients with acute respiratory distress syndrome with or without spontaneous breathing and to investigate whether the effects of spontaneous breathing on outcome depend on acute respiratory distress syndrome severity. DESIGN: Planned secondary analysis of a prospective, observational, multicentre cohort study. SETTING: International sample of 459 ICUs from 50 countries. PATIENTS: Patients with acute respiratory distress syndrome and at least 2 days of invasive mechanical ventilation and available data for the mode of mechanical ventilation and respiratory rate for the 2 first days. INTERVENTIONS: Analysis of patients with and without spontaneous breathing, defined by the mode of mechanical ventilation and by actual respiratory rate compared with set respiratory rate during the first 48 hours of mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Spontaneous breathing was present in 67% of patients with mild acute respiratory distress syndrome, 58% of patients with moderate acute respiratory distress syndrome, and 46% of patients with severe acute respiratory distress syndrome. Patients with spontaneous breathing were older and had lower acute respiratory distress syndrome severity, Sequential Organ Failure Assessment scores, ICU and hospital mortality, and were less likely to be diagnosed with acute respiratory distress syndrome by clinicians. In adjusted analysis, spontaneous breathing during the first 2 days was not associated with an effect on ICU or hospital mortality (33% vs 37%; odds ratio, 1.18 [0.92-1.51]; p = 0.19 and 37% vs 41%; odds ratio, 1.18 [0.93-1.50]; p = 0.196, respectively ). Spontaneous breathing was associated with increased ventilator-free days (13 [0-22] vs 8 [0-20]; p = 0.014) and shorter duration of ICU stay (11 [6-20] vs 12 [7-22]; p = 0.04). CONCLUSIONS: Spontaneous breathing is common in patients with acute respiratory distress syndrome during the first 48 hours of mechanical ventilation. Spontaneous breathing is not associated with worse outcomes and may hasten liberation from the ventilator and from ICU. Although these results support the use of spontaneous breathing in patients with acute respiratory distress syndrome independent of acute respiratory distress syndrome severity, the use of controlled ventilation indicates a bias toward use in patients with higher disease severity. In addition, because the lack of reliable data on inspiratory effort in our study, prospective studies incorporating the magnitude of inspiratory effort and adjusting for all potential severity confounders are required.

Plasma and tissue pharmacokinetics of fosfomycin in morbidly obese and non-obese surgical patients: a controlled clinical trial.

OBJECTIVES: To assess the pharmacokinetics and tissue penetration of fosfomycin in obese and non-obese surgical patients. METHODS: Fifteen obese patients undergoing bariatric surgery and 15 non-obese patients undergoing major intra-abdominal surgery received an intravenous single short infusion of 8 g of fosfomycin. Fosfomycin concentrations were determined by LC-MS/MS in plasma and microdialysate from subcutaneous tissue up to 8 h after dosing. The pharmacokinetic analysis was performed in plasma and interstitial fluid (ISF) by non-compartmental methods. RESULTS: Thirteen obese patients (BMI 38-50 kg/m2) and 14 non-obese patients (BMI 0-29 kg/m2) were evaluable. The pharmacokinetics of fosfomycin in obese versus non-obese patients were characterized by lower peak plasma concentrations (468 ±âŸ139 versus 594 ±âŸ149 mg/L, P = 0.040) and higher V (24.4 ±âŸ6.4 versus 19.0 ±âŸ3.1 L, P = 0.010). The differences in AUC∞ were not significant (1275 ±âŸ477 versus 1515 ±âŸ352 mg·h/L, P = 0.16). The peak concentrations in subcutaneous tissue were reached rapidly and declined in parallel with the plasma concentrations. The drug exposure in tissue was nearly halved in obese compared with non-obese patients (AUC∞ 1052 ±âŸ394 versus 1929 ±âŸ725 mg·h/L, P = 0.0010). The tissue/plasma ratio (AUCISF/AUCplasma) was 0.86 ±âŸ0.32 versus 1.27 ±âŸ0.34 (P = 0.0047). CONCLUSIONS: Whereas the pharmacokinetics of fosfomycin in plasma of surgical patients were only marginally different between obese and non-obese patients, the drug exposure in subcutaneous tissue was significantly lower in the obese patients.