Effect of Intraoperative Goal-directed Balanced Crystalloid versus Colloid Administration on Major Postoperative Morbidity

BACKGROUND: Crystalloid solutions leave the circulation quickly, whereas colloids remain for hours, thus promoting hemodynamic stability. However, colloids are expensive and promote renal toxicity in critical care patients. This study tested the hypothesis that goal-directed colloid administration during elective abdominal surgery decreases 30-day major complications more than goal-directed crystalloid administration. METHODS: In this parallel-arm double-blinded multicenter randomized trial, adults having moderate- to high-risk open and laparoscopically assisted abdominal surgery with general anesthesia were randomly assigned to Doppler-guided intraoperative volume replacement with 6% hydroxyethyl starch 130/0.4 (n = 523) or lactated Ringer's solution (n = 534). The primary outcome was a composite of serious postoperative cardiac, pulmonary, infectious, gastrointestinal, renal, and coagulation complications that were assessed with a generalized estimating equation multivariate model. The primary safety outcome was a change in serum creatinine concentration up to 6 months postoperatively, compared to baseline concentrations. RESULTS: A total of 1,057 patients were included in the analysis. Patients assigned to crystalloid received a median [quartile 1, quartile 3] amount of 3.2 l [2.3, 4.4] of crystalloid, and patients assigned to colloid received 1.0 l [0.5, 1.5] of colloid and 1.8 l [1.2, 2.4] of crystalloid. The estimated intention-to-treat common effect relative risk for the primary composite was 0.90 for colloids versus crystalloids (95% CI: 0.65 to 1.23, P = 0.51), and 18% (91 of 523) of colloid patients and 20% (103 of 534) of crystalloid patients incurred at least one component of the primary outcome composite. There was no evidence of renal toxicity at any time. CONCLUSIONS: Doppler-guided intraoperative hydroxyethyl starch administration did not significantly reduce a composite of serious complications. However, there was also no indication of renal or other toxicity

Differential effects of antibiotics in combination with G-CSF on survival and polymorphonuclear granulocyte cell functions in septic rats

<p>Abstract</p> <p>Background</p> <p>In addition to their antimicrobial activity, antibiotics modulate cellular host defence. Granulocyte-colony stimulating factor (G-CSF) is also a well known immunomodulator; however little is known about the interactions of G-CSF with antibiotics. We investigated in septic rats the effects of two antibiotic combinations with G-CSF.</p> <p>Methods</p> <p>In two clinic modelling randomised trials (CMRTs), male Wistar rats were anesthetized, given antibiotic prophylaxis, had a laparotomy with peritoneal contamination and infection (PCI), and were randomly assigned (n = 18 rats/group) to: 1) PCI only; 2) PCI+antibiotic; and, 3) PCI+antibiotic+G-CSF prophylaxis (20 μg/kg, three times). This sequence was conducted first with 10 mg/kg coamoxiclav, and then with ceftriaxone/metronidazole (Cef/met, 10/3 mg/kg). In additional animals, the blood cell count, migration and superoxide production of PMNs, systemic TNF-α and liver cytokine mRNA expression levels were determined.</p> <p>Results</p> <p>Only the combination coamoxiclav plus G-CSF improved the survival rate (82 vs. 44%, p < 0.001). Improved survival with this combination was accompanied by normalised antimicrobial PMN migratory activity and superoxide production, along with normalised systemic TNF-α levels and a reduced expression of TNF-α and IL-1 in the liver.</p> <p>Conclusion</p> <p>There are substantial differences in the interaction of antibiotics with G-CSF. Therefore, the selection of the antibiotic for combination with G-CSF in sepsis treatment should be guided not only by the bacteria to be eliminated, but also by the effects on antimicrobial functions of PMNs and the cytokine response.</p

Stability of Propofol (2,6-Diisopropylphenol) in Thermal Desorption Tubes during Air Transport

The anesthetic propofol and other exhaled organic compounds can be sampled in Tenax sorbent tubes and analyzed by gas chromatography coupled with mass spectrometry. The aim of this study was to evaluate the stability of propofol in Tenax sorbent tubes during overseas shipping. This is relevant for international pharmacokinetic studies on propofol in exhaled air. Tenax sorbent tube propofol samples with concentrations between 10 and 100 ng were prepared by liquid injection and with a calibration gas generator. For each preparation method, one reference set was analyzed immediately after preparation, a second set was stored at room temperature, and a third one was stored refrigerated. The fourth set was sent from Germany by airmail to USA and back. The shipped set of tubes was analyzed when it returned after 55 days elapsed. Then, the room temperature samples and the refrigerated stored samples were also analyzed. To evaluate the stability of propofol in the stored and shipped tubes, we calculated the recovery rates of each sample set. The mean recovery in the stored samples was 101.2% for the liquid preparation and 134.6% for the gaseous preparation at 4°C. At 22°C, the recovery was 96.1% for liquid preparation and 92.1% for gaseous preparation, whereas the shipped samples had a recovery of 85.3% and 111.3%. Thus, the deviation of the shipped samples is within a range of 15%, which is analytically acceptable. However, the individual values show significantly larger deviations of up to -32.1% (liquid) and 30.9% (gaseous). We conclude that storage of propofol on Tenax tubes at room temperature for 55 days is possible to obtain acceptable results. However, it appears that due to severe temperature and pressure variations air shipment of propofol samples in Tenax tubes without cooling shows severe deviations from the initial concentration. Although it was not tested in this study, we assume that refrigerated transport might be necessary to obtain comparable results as in the stored samples

Stability of Propofol (2,6-Diisopropylphenol) in Thermal Desorption Tubes during Air Transport

The anesthetic propofol and other exhaled organic compounds can be sampled in Tenax sorbent tubes and analyzed by gas chromatography coupled with mass spectrometry. The aim of this study was to evaluate the stability of propofol in Tenax sorbent tubes during overseas shipping. This is relevant for international pharmacokinetic studies on propofol in exhaled air. Tenax sorbent tube propofol samples with concentrations between 10 and 100 ng were prepared by liquid injection and with a calibration gas generator. For each preparation method, one reference set was analyzed immediately after preparation, a second set was stored at room temperature, and a third one was stored refrigerated. The fourth set was sent from Germany by airmail to USA and back. The shipped set of tubes was analyzed when it returned after 55 days elapsed. Then, the room temperature samples and the refrigerated stored samples were also analyzed. To evaluate the stability of propofol in the stored and shipped tubes, we calculated the recovery rates of each sample set. The mean recovery in the stored samples was 101.2% for the liquid preparation and 134.6% for the gaseous preparation at 4°C. At 22°C, the recovery was 96.1% for liquid preparation and 92.1% for gaseous preparation, whereas the shipped samples had a recovery of 85.3% and 111.3%. Thus, the deviation of the shipped samples is within a range of 15%, which is analytically acceptable. However, the individual values show significantly larger deviations of up to -32.1% (liquid) and 30.9% (gaseous). We conclude that storage of propofol on Tenax tubes at room temperature for 55 days is possible to obtain acceptable results. However, it appears that due to severe temperature and pressure variations air shipment of propofol samples in Tenax tubes without cooling shows severe deviations from the initial concentration. Although it was not tested in this study, we assume that refrigerated transport might be necessary to obtain comparable results as in the stored samples

Aggressive intraoperative warming and postoperative pulmonary complications in elderly patients recovering from esophageal cancer surgery: sub-analysis of a randomized trial

BackgroundElderly patients having esophagectomies often become hypothermic which may promote complications. We tested the hypothesis that aggressive warming to a core temperature of 37°C reduces postoperative pulmonary complications (PPCs) in elderly patients having esophageal cancer resections.MethodsThis study was a pre-defined sub-study of a multi-center, parallel group, superiority trial (PROTECT). Patients aged &gt;65 years and having elective radical resection of esophageal cancer in a single center were randomly allocated into either aggressive warming group (target intraoperative core temperatures of 37°C) or routine thermal management group (target intraoperative core temperatures of 35.5°C). The primary endpoint was the incidence of PPCs. Secondary endpoints included duration of chest tube drainage and other postoperative complications.ResultsA total of 300 patients were included in the primary analysis. PPCs occurred in 27 (18%) of 150 patients in the aggressive warming group and 31 (21%) of 150 patients in the routine thermal management group. The relative risk (RR) of aggressive versus routine thermal management was 0.9 (95% CI: 0.5, 1.4; p = 0.56). The duration of chest drainage in patients assigned to aggressive warming was shorter than that assigned to routine thermal management: 4 (3, 5) days vs. 5 (4, 7) days; hazard ratio (HR) 1.4 [95% CI: 1.1, 1.7]; p = 0.001. Fewer aggressively warmed patients needed chest drainage for more than 5 days: 30/150 (20%) vs. 51/150 (34%); RR:0.6 (95% CI: 0.4, 0.9; p = 0.03). The incidence of other postoperative complications were similar between the two groups.ConclusionAggressive warming does not reduce the incidence of PPCs in elderly patients receiving esophagectomy. The duration of chest drainage was reduced by aggressive warming. But as a secondary analysis of a planned sub-group study, these results should be considered exploratory.Clinical trial registrationhttps://www.chictr.org.cn/showproj.aspx?proj=37099, ChiCTR1900022257

Endotracheal tube cuff pressure in three hospitals, and the volume required to produce an appropriate cuff pressure

BACKGROUND: Cuff pressure in endotracheal (ET) tubes should be in the range of 20–30 cm H(2)O. We tested the hypothesis that the tube cuff is inadequately inflated when manometers are not used. METHODS: With IRB approval, we studied 93 patients under general anesthesia with an ET tube in place in one teaching and two private hospitals. Anesthetists were blinded to study purpose. Cuff pressure in tube sizes 7.0 to 8.5 mm was evaluated 60 min after induction of general anesthesia using a manometer connected to the cuff pilot balloon. Nitrous oxide was disallowed. After deflating the cuff, we reinflated it in 0.5-ml increments until pressure was 20 cmH(2)O. RESULTS: Neither patient morphometrics, institution, experience of anesthesia provider, nor tube size influenced measured cuff pressure (35.3 ± 21.6 cmH(2)O). Only 27% of pressures were within 20–30 cmH(2)O; 27% exceeded 40 cmH(2)O. Although it varied considerably, the amount of air required to achieve a cuff pressure of 20 cmH(2)O was similar with each tube size. CONCLUSION: We recommend that ET cuff pressure be set and monitored with a manometer

Residual volatile anesthetics after workstation preparation and activated charcoal filtration

Background Volatile anesthetics potentially trigger malignant hyperthermia crises in susceptible patients. We therefore aimed to identify preparation procedures for the Draeger Primus that minimize residual concentrations of desflurane and sevoflurane with and without activated charcoal filtration. Methods A Draeger Primus test workstation was primed with 7% desflurane or 2.5% sevoflurane for 2 hours. Residual anesthetic concentrations were evaluated with five preparation procedures, three fresh gas flow rates, and three distinct applications of activated charcoal filters. Finally, non‐exchangeable and autoclaved parts of the workstation were tested for residual emission of volatile anesthetics. Concentrations were measured by multicapillary column–ion mobility spectrometry with limits of detection/quantification being <1 part per billion (ppb) for desflurane and <2.5 ppb for sevoflurane. Results The best preparation procedure included a flushing period of 10 minutes between removal and replacement of all parts of the ventilator circuit which immediately produced residual concentrations <5 ppm. A fresh gas flow of 10 L/minute reduced residual concentration as effectively as 18 L/minute, whereas flows of 1 or 5 L/minute slowed washout. Use of activated charcoal filters immediately reduced and maintained residual concentrations <5 ppm for up to 24 hours irrespective of previous workstation preparation. The fresh gas hose, circle system, and ventilator diaphragm emitted traces of volatile anesthetics. Conclusion In elective cases, presumably safe concentrations can be obtained by a 10‐minute flush at ≥10 L/minute between removal and replacement all components of the airway circuit. For emergencies, we recommend using an activated charcoal filter

Quantification of Volatile Aldehydes Deriving from In Vitro Lipid Peroxidation in the Breath of Ventilated Patients

Exhaled aliphatic aldehydes were proposed as non-invasive biomarkers to detect increased lipid peroxidation in various diseases. As a prelude to clinical application of the multicapillary column–ion mobility spectrometry for the evaluation of aldehyde exhalation, we, therefore: (1) identified the most abundant volatile aliphatic aldehydes originating from in vitro oxidation of various polyunsaturated fatty acids; (2) evaluated emittance of aldehydes from plastic parts of the breathing circuit; (3) conducted a pilot study for in vivo quantification of exhaled aldehydes in mechanically ventilated patients. Pentanal, hexanal, heptanal, and nonanal were quantifiable in the headspace of oxidizing polyunsaturated fatty acids, with pentanal and hexanal predominating. Plastic parts of the breathing circuit emitted hexanal, octanal, nonanal, and decanal, whereby nonanal and decanal were ubiquitous and pentanal or heptanal not being detected. Only pentanal was quantifiable in breath of mechanically ventilated surgical patients with a mean exhaled concentration of 13 ± 5 ppb. An explorative analysis suggested that pentanal exhalation is associated with mechanical power—a measure for the invasiveness of mechanical ventilation. In conclusion, exhaled pentanal is a promising non-invasive biomarker for lipid peroxidation inducing pathologies, and should be evaluated in future clinical studies, particularly for detection of lung injury

Isoflurane promotes early spontaneous breathing in ventilated intensive care patients: A post hoc subgroup analysis of a randomized trial

Background: Spontaneous breathing is desirable in most ventilated patients. We therefore studied the influence of isoflurane versus propofol sedation on early spon taneous breathing in ventilated surgical intensive care patients and evaluated poten tial mediation by opioids and arterial carbon dioxide during the first 20 h of study sedation. Methods: We included a single-center subgroup of 66 patients, who participated in a large multi-center trial assessing efficacy and safety of isoflurane sedation, with 33 patients each randomized to isoflurane or propofol sedation. Both sedatives were titrated to a sedation depth of −4 to −1 on the Richmond Agitation Sedation Scale. The primary outcome was the fraction of time during which patients breathed spontaneously. Results: Baseline characteristics of isoflurane and propofol-sedated patients were well balanced. There were no substantive differences in management or treatment aside from sedation, and isoflurane and propofol provided nearly identical sedation depths. The mean fraction of time spent spontaneously breathing was 82% [95% CI: 69, 90] in patients sedated with isoflurane compared to 35% [95% CI: 22, 51] in those assigned to propofol: median difference: 61% [95% CI: 14, 89], p < .001. After ad justments for sufentanil dose and arterial carbon dioxide partial pressure, patients sedated with isoflurane were twice as likely to breathe spontaneously than those se dated with propofol: adjusted risk ratio: 2.2 [95%CI: 1.4, 3.3], p < .001. Conclusions: Isoflurane compared to propofol sedation promotes early spontaneous breathing in deeply sedated ventilated intensive care patients. The benefit appears to be a direct effect isoflurane rather than being mediated by opioids or arterial carbon dioxide