Christopher Uhlig

Higher levels of spontaneous breathing induce lung recruitment and reduce global stress/strain in experimental lung injury.

Background:Spontaneous breathing (SB) in the early phase of the acute respiratory distress syndrome is controversial. Biphasic positive airway pressure/airway pressure release ventilation (BIPAP/APRV) is commonly used, but the level of SB necessary to maximize potential beneficial effects is unknown. Methods:Experimental acute respiratory distress syndrome was induced by saline lung lavage in anesthetized and mechanically ventilated pigs (n = 12). By using a Latin square and crossover design, animals were ventilated with BIPAP/APRV at four different levels of SB in total minute ventilation (60 min each): (1) 0% (BIPAP/APRV0%); (2) greater than 0 to 30% (BIPAP/APRV>0–30%); (3) greater than 30 to 60% (BIPAP/APRV>30–60%); and (4) greater than 60% (BIPAP/APRV>60%). Gas exchange, hemodynamics, and respiratory variables were measured. Lung aeration was assessed by high-resolution computed tomography. The distribution of perfusion was marked with 68Ga-labeled microspheres and evaluated by positron emission tomography. Results:The authors found that higher levels of SB during BIPAP/APRV (1) improved oxygenation; (2) decreased mean transpulmonary pressure (stress) despite increased inspiratory effort; (3) reduced nonaerated lung tissue, with minimal changes in the distribution of perfusion, resulting in decreased low aeration/perfusion zones; and (4) decreased global strain (mean ± SD) (BIPAP/APRV0%: 1.39 ± 0.08; BIPAP/APRV0–30%: 1.33 ± 0.03; BIPAP/APRV30–60%: 1.27 ± 0.06; BIPAP/APRV>60%: 1.25 ± 0.04, P < 0.05 all vs. BIPAP/APRV0%, and BIPAP/APRV>60% vs. BIPAP/APRV0–30%). Conclusions:In a saline lung lavage model of experimental acute respiratory distress syndrome in pigs, levels of SB during BIPAP/APRV higher than currently recommended for clinical practice, that is, 10 to 30%, improve oxygenation by increasing aeration in dependent lung zones without relevant redistribution of perfusion. In presence of lung recruitment, higher levels of SB reduce global stress and strain despite an increase in inspiratory effort.

Effects of Volatile Anesthetics on Mortality and Postoperative Pulmonary and Other Complications in Patients Undergoing Surgery: A Systematic Review and Meta-analysis

Background:It is not known whether modern volatile anesthetics are associated with less mortality and postoperative pulmonary or other complications in patients undergoing general anesthesia for surgery. Methods:A systematic literature review was conducted for randomized controlled trials fulfilling following criteria: (1) population: adult patients undergoing general anesthesia for surgery; (2) intervention: patients receiving sevoflurane, desflurane, or isoflurane; (3) comparison: volatile anesthetics versus total IV anesthesia or volatile anesthetics; (4) reporting on: (a) mortality (primary outcome) and (b) postoperative pulmonary or other complications; (5) study design: randomized controlled trials. The authors pooled treatment effects following Peto odds ratio (OR) meta-analysis and network meta-analysis methods. Results:Sixty-eight randomized controlled trials with 7,104 patients were retained for analysis. In cardiac surgery, volatile anesthetics were associated with reduced mortality (OR = 0.55; 95% CI, 0.35 to 0.85; P = 0.007), less pulmonary (OR = 0.71; 95% CI, 0.52 to 0.98; P = 0.038), and other complications (OR = 0.74; 95% CI, 0.58 to 0.95; P = 0.020). In noncardiac surgery, volatile anesthetics were not associated with reduced mortality (OR = 1.31; 95% CI, 0.83 to 2.05, P = 0.242) or lower incidences of pulmonary (OR = 0.67; 95% CI, 0.42 to 1.05; P = 0.081) and other complications (OR = 0.70; 95% CI, 0.46 to 1.05; P = 0.092). Conclusions:In cardiac, but not in noncardiac, surgery, when compared to total IV anesthesia, general anesthesia with volatile anesthetics was associated with major benefits in outcome, including reduced mortality, as well as lower incidence of pulmonary and other complications. Further studies are warranted to address the impact of volatile anesthetics on outcome in noncardiac surgery.

Albumin versus crystalloid solutions in patients with the acute respiratory distress syndrome: a systematic review and meta-analysis.

IntroductionIn patients with acute respiratory distress syndrome (ARDS) fluid therapy might be necessary. The aim of this systematic review and meta-analysis is to determine the effects of colloid therapy compared to crystalloids on mortality and oxygenation in adults with ARDS.MethodsRandomized controlled trials (RCTs) were identified through a systematic literature search of MEDLINE, EMBASE, CENTRAL and LILACS. Articles published up to 15th February 2013 were independently screened, abstracted, and assessed (Cochrane Risk of Bias Tool) to provide evidence-based therapy recommendations. RCTs were eligible if they compared colloid versus crystalloid therapy on lung function, inflammation, damage or mortality in adults with ARDS. Primary outcome parameters were respiratory mechanics, gas exchange lung inflammation and damage as well as hospital mortality. Kidney function, need for renal replacement therapy, hemodynamic stabilization and intensive care unit (ICU) length of stay served as secondary outcomes.ResultsA total of 3 RCTs out of 4130 potential trials found in the databases were selected for qualitative and quantitative analysis totaling 206 patients who received either albumin or saline. Overall risk of bias was unclear to high in the identified trials. Calculated pooled risk of death was not statistically significant (albumin 34 of 100 (34.0%) versus 40 of 104 (38.5%), relative risk (RR) = 0.89, 95% confidence interval (CI) 0.62 to 1.28, P = 0.539). Weighted mean difference (WMD) in PaO2/FiO2 (mmHg) improved in the first 48 hours (WMD = 62, 95% CI 47 to 77, P <0.001, I2 = 0%) after therapy start and remained stable after 7 days (WMD = 20, 95% CI 4 to 36, P = 0.017, I2 = 0%).ConclusionsThere is a high need for RCTs investigating the effects of colloids in ARDS patients. Based on the findings of this review, colloid therapy with albumin improved oxygenation but did not affect mortality.

Effects of intravascular volume replacement on lung and kidney function and damage in nonseptic experimental lung injury.

Background:Intravascular volume replacement is often required in the presence of increased pulmonary capillary leakage, for example in patients with volutrauma with major hemorrhage. In the present study, the effects of Ringer’s acetate (RA), gelatin-polysuccinate (GEL), and a modern hydroxyethyl starch (HES, 6% 130/0.42) on lung and kidney function and damage were compared in a two-hit model of acute lung injury. The authors hypothesized that GEL and HES, compared to RA: (1) reduced lung histological damage, (2) impaired kidney morphology and function. Methods:Acute lung injury was induced in 30 anesthetized pigs by tidal volumes approximately 40 ml/kg, after saline lung lavage. Protective ventilation was initiated and approximately≈25% of estimated blood volume was drawn. Animals were randomly assigned to receive RA, GEL, or HES (n = 10/group) aimed at approximately 90% of intrathoracic blood volume before blood drainage. Results:Fluid volumes were higher with RA (2,250 ± 764 ml) than GEL (704 ± 159 ml) and HES (837 ± 82 ml) (P < 0.05). Compared to RA, HES reduced diffuse alveolar damage overall, and GEL in nondependent zones only. GEL and HES yielded lower wet-to-dry ratios compared to RA (6.5 ± 0.5 and 6.5 ± 0.6 vs. 7.9 ± 0.9, respectively, P < 0.05). HES and RA resulted in less kidney damage than GEL, but kidney function did not differ significantly among groups. Compared to GEL, HES yielded lower lung elastance (55 ± 12 vs. 45 ± 13 cm H2O/l, P < 0.05) and intra-abdominal pressure (15 ± 5 vs. 11 ± 4 cm 14;H2O, P < 0.05). Conclusions:In this model of acute lung injury, intravascular volume expansion after major hemorrhage with HES yielded less lung damage than RA and less kidney damage than GEL.

Effects of assisted and variable mechanical ventilation on cardiorespiratory interactions in anesthetized pigs

The physiological importance of respiratory sinus arrhythmia (RSA) and cardioventilatory coupling (CVC) has not yet been fully elucidated, but these phenomena might contribute to improve ventilation/perfusion matching, with beneficial effects on gas exchange. Furthermore, decreased RSA amplitude has been suggested as an indicator of impaired autonomic control and poor clinical outcome, also during positive-pressure mechanical ventilation (MV). However, it is currently unknown how different modes of MV, including variable tidal volumes (V(T)), affect RSA and CVC during anesthesia. We compared the effects of pressure controlled (PCV) versus pressure assisted (PSV) ventilation, and of random variable versus constant V(T), on RSA and CVC in eight anesthetized pigs. At comparable depth of anesthesia, global hemodynamics, and ventilation, RSA amplitude increased from 20 ms in PCV to 50 ms in PSV (p < 0.05). CVC was detected (using proportional Shannon entropy of the interval between each inspiration onset and the previous R-peak in ECG) in two animals in PCV and seven animals in PSV. Variable V(T) did not significantly influence these phenomena. Furthermore, heart period and systolic arterial pressure oscillations were in phase during PCV but in counter-phase during PSV. At the same depth of anesthesia in pigs, PSV increases RSA amplitude and CVC compared to PCV. Our data suggest that the central respiratory drive, but not the baroreflex or the mechano-electric feedback in the heart, is the main mechanism behind the RSA increase. Hence, differences in RSA and CVC between mechanically ventilated patients might reflect the difference in ventilation mode rather than autonomic impairment. Also, since gas exchange did not increase from PCV to PSV, it is questionable whether RSA has any significance in improving ventilation/perfusion matching during MV.

Effects of Ultraprotective Ventilation, Extracorporeal Carbon Dioxide Removal, and Spontaneous Breathing on Lung Morphofunction and Inflammation in Experimental Severe Acute Respiratory Distress Syndrome

Background:To investigate the role of ultraprotective mechanical ventilation (UP-MV) and extracorporeal carbon dioxide removal with and without spontaneous breathing (SB) to improve respiratory function and lung protection in experimental severe acute respiratory distress syndrome. Methods:Severe acute respiratory distress syndrome was induced by saline lung lavage and mechanical ventilation (MV) with higher tidal volume (VT) in 28 anesthetized pigs (32.8 to 52.5 kg). Animals (n = 7 per group) were randomly assigned to 6 h of MV (airway pressure release ventilation) with: (1) conventional P-MV with VT ≈6 ml/kg (P-MVcontr); (2) UP-MV with VT ≈3 ml/kg (UP-MVcontr); (3) UP-MV with VT ≈3 ml/kg and SB (UP-MVspont); and (4) UP-MV with VT ≈3 ml/kg and pressure supported SB (UP-MVPS). In UP-MV groups, extracorporeal carbon dioxide removal was used. Results:The authors found that: (1) UP-MVcontr reduced diffuse alveolar damage score in dorsal lung zones (median[interquartile]) (12.0 [7.0 to 16.8] vs. 22.5 [13.8 to 40.8]), but worsened oxygenation and intrapulmonary shunt, compared to P-MVcontr; (2) UP-MVspont and UP-MVPS improved oxygenation and intrapulmonary shunt, and redistributed ventilation towards dorsal areas, as compared to UP-MVcontr; (3) compared to P-MVcontr, UP-MVcontr and UP-MVspont, UP-MVPS yielded higher levels of tumor necrosis factor-&agr; (6.9 [6.5 to 10.1] vs. 2.8 [2.2 to 3.0], 3.6 [3.0 to 4.7] and 4.0 [2.8 to 4.4] pg/mg, respectively) and interleukin-8 (216.8 [113.5 to 343.5] vs. 59.8 [45.3 to 66.7], 37.6 [18.8 to 52.0], and 59.5 [36.1 to 79.7] pg/mg, respectively) in dorsal lung zones. Conclusions:In this model of severe acute respiratory distress syndrome, MV with VT ≈3 ml/kg and extracorporeal carbon dioxide removal without SB slightly reduced lung histologic damage, but not inflammation, as compared to MV with VT = 4 to 6 ml/kg. During UP-MV, pressure supported SB increased lung inflammation.

Anesthesia and Monitoring in Small Laboratory Mammals Used in Anesthesiology, Respiratory and Critical Care Research: A Systematic Review on the Current Reporting in Top-10 Impact Factor Ranked Journals

Rationale This study aimed to investigate the quality of reporting of anesthesia and euthanasia in experimental studies in small laboratory mammals published in the top ten impact factor journals. Methods A descriptive systematic review was conducted and data was abstracted from the ten highest ranked journals with respect to impact factor in the categories ‘Anesthesiology’, ‘Critical Care Medicine’ and ‘Respiratory System’ as defined by the 2012 Journal Citation Reports. Inclusion criteria according to PICOS criteria were as follows: 1) population: small laboratory mammals; 2) intervention: any form of anesthesia and/or euthanasia; 3) comparison: not specified; 4) primary outcome: type of anesthesia, anesthetic agents and type of euthanasia; secondary outcome: animal characteristics, monitoring, mechanical ventilation, fluid management, postoperative pain therapy, animal care approval, sample size calculation and performed interventions; 5) study: experimental studies. Anesthesia, euthanasia, and monitoring were analyzed per performed intervention in each article. Results The search yielded 845 articles with 1,041 interventions of interest. Throughout the manuscripts we found poor quality and frequency of reporting with respect to completeness of data on animal characteristics as well as euthanasia, while anesthesia (732/1041, 70.3%) and interventions without survival (970/1041, 93.2%) per se were frequently reported. Premedication and neuromuscular blocking agents were reported in 169/732 (23.1%) and 38/732 (5.2%) interventions, respectively. Frequency of reporting of analgesia during (117/610, 19.1%) and after painful procedures (38/364, 10.4%) was low. Euthanasia practice was reported as anesthesia (348/501, 69%), transcardial perfusion (37/501, 8%), carbon dioxide (26/501, 6%), decapitation (22/501, 5%), exsanguination (23/501, 5%), other (25/501, 5%) and not specified (20/501, 4%, respectively. Conclusions The present systematic review revealed insufficient reporting of anesthesia and euthanasia methods throughout experimental studies in small laboratory mammals. Specific guidelines for anesthesia and euthanasia regimens should be considered to achieve comparability, quality of animal experiments and animal welfare. These measures are of special interest when translating experimental findings to future clinical applications.

Variable versus conventional lung protective mechanical ventilation during open abdominal surgery (PROVAR): a randomised controlled trial

Background: Experimental studies showed that controlled variable ventilation (CVV) yielded better pulmonary function compared to non‐variable ventilation (CNV) in injured lungs. We hypothesized that CVV improves intraoperative and postoperative respiratory function in patients undergoing open abdominal surgery. Methods: Fifty patients planned for open abdominal surgery lasting >3 h were randomly assigned to receive either CVV or CNV. Mean tidal volumes and PEEP were set at 8 ml kg−1 (predicted body weight) and 5 cm H2O, respectively. In CVV, tidal volumes varied randomly, following a normal distribution, on a breath‐by‐breath basis. The primary endpoint was the forced vital capacity (FVC) on postoperative Day 1. Secondary endpoints were oxygenation, non‐aerated lung volume, distribution of ventilation, and pulmonary and extrapulmonary complications until postoperative Day 5. Results: FVC did not differ significantly between CVV and CNV on postoperative Day 1, 61.5 (standard deviation 22.1) % vs 61.9 (23.6) %, respectively; mean [95% confidence interval (CI)] difference, −0.4 (−13.2–14.0), P=0.95. Intraoperatively, CVV did not result in improved respiratory function, haemodynamics, or redistribution of ventilation compared to CNV. Postoperatively, FVC, forced expiratory volume at the first second (FEV1), and FEV1/FVC deteriorated, while atelectasis volume and plasma levels of interleukin‐6 and interleukin‐8 increased, but values did not differ between groups. The incidence of postoperative pulmonary and extrapulmonary complications was comparable in CVV and CNV. Conclusions: In patients undergoing open abdominal surgery, CVV did not improve intraoperative and postoperative respiratory function compared with CNV. Clinical trial registration: NCT 01683578.

Comments on Kagan et al.: Preemptive enteral nutrition enriched with eicosapentaenoic acid, gamma-linolenic acid and antioxidants in severe multiple trauma: a prospective, randomized, double-blind study

Dear Editor, We read with great interest the manuscript by Kagan and colleagues regarding early enteral nutrition enriched with omega-3 polyunsaturated fatty acids in intensive care unit patients suffering from severe multiple trauma [1]. In severe trauma, systemic inflammatory response may induce multiorgan failure. Omega-3 polyunsaturated fatty acids (x-3 PUFAs) have shown to resolve the effects in ARDS [2] and sepsis [3]. The key concept of x-3 PUFA use is limitation of the overwhelming inflammatory reaction at the earliest possible point in time to cover the peak of the inflammatory response in the first 3–4 days after onset of trauma. The integration of x-3 PUFAs into the cellular membrane is the precondition for their metabolism which results in the desired anti-hyperinflammatory effects. Thus, administration x-3 PUFAs must commence at the earliest possible point in time. As demonstrated earlier [4], the intestinal resorption of x-3 PUFAs is not sufficient in all patients during systemic inflammation. The enteral application form chosen in the study protocol led to too slow a buildup of x-3 PUFA pool with respect to the chosen enteral dosage. Not till the fourth day was a measurable increase of x-3 PUFA detected in the cellular membrane. Over the time course of the trial no clinically significant x-3 PUFA indexes were reached which would be expected to exert any beneficial effects. An intravenous route with adaptable dosage should have been the preferred approach in the acute phase as used in the ongoing FOILED study (NCT01146821). In addition, the negative results could also be explained by the fact that the group treated with x-3 PUFA had a higher rate of multiple trauma patients [57 (91.9 %) vs. 45 (77.6 %), respectively, P = 0.04], resulting in a higher rate of packed red blood cell transfusions (189 vs. 77 units, respectively, P = 0.03) compared to controls. Therefore, the results of this study should be interpreted with caution. The trial by Kagan and colleagues demonstrates once more that absence of evidence is not evidence of absence.