Background The combination of complete diaphragm inactivity and mechanical ventilation (for more than 18 hours) elicits disuse atrophy of myofibers in animals. We hypothesized that the same may also occur in the human diaphragm. Methods We obtained biopsy specimens from the costal diaphragms of 14 brain-dead organ donors before organ harvest (case subjects) and compared them with intraoperative biopsy specimens from the diaphragms of 8 patients who were undergoing surgery for either benign lesions or localized lung cancer (control subjects). Case subjects had diaphragmatic inactivity and underwent mechanical ventilation for 18 to 69 hours; among control subjects diaphragmatic inactivity and mechanical ventilation were limited to 2 to 3 hours. We carried out histologic, biochemical, and gene-expression studies on these specimens. Results As compared with diaphragm-biopsy specimens from controls, specimens from case subjects showed decreased cross-sectional areas of slow-twitch and fast-twitch fibers of 57% (P = 0.001) and 53% (P = 0.01), respectively, decreased glutathione concentration of 23% (P = 0.01), increased active caspase-3 expression of 100% (P = 0.05), a 200% higher ratio of atrogin-1 messenger RNA (mRNA) transcripts to MBD4 (a housekeeping gene) (P = 0.002), and a 590% higher ratio of MuRF-1 mRNA transcripts to MBD4 (P = 0.001). Conclusions The combination of 18 to 69 hours of complete diaphragmatic inactivity and mechanical ventilation results in marked atrophy of human diaphragm myofibers. These findings are consistent with increased diaphragmatic proteolysis during inactivity.

https://www.nejm.org/doi/pdf/10.1056/NEJMoa070447

Rapid disuse atrophy of diaphragm fibers in mechanically ventilated humans.

Background:How best to characterize intraoperative hypotension remains unclear Thus, the authors assessed the relationship between myocardial and kidney injury and intraoperative absolute (mean arterial pressure [MAP]) and relative (reduction from preoperative pressure) MAP thresholdsMethods:The a

Relationship between Intraoperative Hypotension, Defined by Either Reduction from Baseline or Absolute Thresholds, and Acute Kidney and Myocardial Injury after Noncardiac Surgery: A Retrospective Cohort Analysis.

Importance Perioperative hypotension is associated with an increase in postoperative morbidity and mortality, but the appropriate management strategy remains uncertain. Objective To evaluate whether an individualized blood pressure management strategy tailored to individual patient physiology could reduce postoperative organ dysfunction. Design, Setting, and Participants The Intraoperative Norepinephrine to Control Arterial Pressure (INPRESS) study was a multicenter, randomized, parallel-group clinical trial conducted in 9 French university and nonuniversity hospitals. Adult patients (n = 298) at increased risk of postoperative complications with a preoperative acute kidney injury risk index of class III or higher (indicating moderate to high risk of postoperative kidney injury) undergoing major surgery lasting 2 hours or longer under general anesthesia were enrolled from December 4, 2012, through August 28, 2016 (last follow-up, September 28, 2016). Interventions Individualized management strategy aimed at achieving a systolic blood pressure (SBP) within 10% of the reference value (ie, patient’s resting SBP) or standard management strategy of treating SBP less than 80 mm Hg or lower than 40% from the reference value during and for 4 hours following surgery. Main Outcomes and Measures The primary outcome was a composite of systemic inflammatory response syndrome and dysfunction of at least 1 organ system of the renal, respiratory, cardiovascular, coagulation, and neurologic systems by day 7 after surgery. Secondary outcomes included the individual components of the primary outcome, durations of ICU and hospital stay, adverse events, and all-cause mortality at 30 days after surgery. Results Among 298 patients who were randomized, 292 patients completed the trial (mean [SD] age, 70 [7] years; 44 [15.1%] women) and were included in the modified intention-to-treat analysis. The primary outcome event occurred in 56 of 147 patients (38.1%) assigned to the individualized treatment strategy vs 75 of 145 patients (51.7%) assigned to the standard treatment strategy (relative risk, 0.73; 95% CI, 0.56 to 0.94;P = .02; absolute risk difference, −14%, 95% CI, −25% to −2%). Sixty-eight patients (46.3%) in the individualized treatment group and 92 (63.4%) in the standard treatment group had postoperative organ dysfunction by day 30 (adjusted hazard ratio, 0.66; 95% CI, 0.52 to 0.84;P = .001). There were no significant between-group differences in severe adverse events or 30-day mortality. Conclusions and Relevance Among patients predominantly undergoing abdominal surgery who were at increased postoperative risk, management targeting an individualized systolic blood pressure, compared with standard management, reduced the risk of postoperative organ dysfunction. Trial Registration clinicaltrials.gov Identifier:NCT01536470

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Effect of Individualized vs Standard Blood Pressure Management Strategies on Postoperative Organ Dysfunction Among High-Risk Patients Undergoing Major Surgery: A Randomized Clinical Trial

Background Intraoperative hypotension (IOH) is a common side effect of general anesthesia and has been reported to be associated with adverse perioperative outcomes. These associations were found using different definitions for IOH. It is unknown whether the incidences of IOH found with those different definitions are comparable. The authors aimed to describe the relation between the chosen definition and incidence of IOH. Methods First, a systematic literature search was performed to identify recent definitions of IOH that have been used in the anesthesia literature. Subsequently, these definitions were applied to a cohort of 15,509 consecutive adult patients undergoing noncardiac surgery during general anesthesia. The incidence of IOH according to the different threshold values was calculated, and the effect of a defined minimal duration of a hypotensive episode was studied. Results Many different definitions of IOH were found. When applied to a cohort of patients, these different definitions resulted in different IOH incidences. Any episode of systolic blood pressure below 80 mmHg was found in 41% of the patients, whereas 93% of the patients had at least one episode of systolic blood pressure more than 20% below baseline. Both definitions are frequently used in the literature. The relation between threshold values from the literature and IOH incidence shows an S-shaped cumulative incidence curve, with occurrence frequencies of IOH varying from 5% to 99%. Conclusions There is no widely accepted definition of IOH. With varying definitions, many different incidences can be reproduced. This might have implications for previously described associations between IOH and adverse outcomes.

/pdf/incidence-of-intraoperative-hypotension-as-a-function-of-the-292zbbehot.pdf

Incidence of intraoperative hypotension as a function of the chosen definition: literature definitions applied to a retrospective cohort using automated data collection.

https://www.gastrojournal.org/article/S0016-5085(09)00999-8/pdf

Endoscopist-Directed Administration of Propofol: A Worldwide Safety Experience

Background: This study describes a nationwide survey that estimates the number and characteristics of anesthesia-related deaths for the year 1999. Methods: Death certificates from the French national mortality database were selected from the International Classification of Diseases, Ninth Revision codes using a variable sampling fraction. Medical certifiers were sent a questionnaire (response rate, 97%), and the anesthesiologist in charge was offered a peer review (acceptance rate, 97%). Files were reviewed to determine the mechanism of each perioperative death and its relation to anesthesia. Mortality rates were calculated using the number of anesthetic procedures estimated from a national 1996 survey and compared with a previous (1978‐1982) nationwide study. Results: Among the 4,200 certificates analyzed, 256 led to a detailed evaluation. The death rates totally or partially related to anesthesia for 1999 were 0.69 in 100,000 (95% confidence interval, 0.22‐1.2 in 100,000) and 4.7 in 100,000 (3.1‐6.3 in 100,000), respectively. The death rate increased from 0.4 to 55 in 100,000 for American Society of Anesthesiologists physical status I and IV patients, respectively. Rates increased with increasing age. Although concerns regarding aspiration of gastric contents remain, intraoperative hypotension and anemia associated with postoperative ischemic complications were the associated factors most often encountered. Deviations from standard practice and organizational failure were often found to be associated with death. Conclusion: In comparison with data from a previous nationwide study (1978‐1982), the anesthesia-related mortality rate in France seems to be reduced 10-fold in 1999. Much remains to be done to improve compliance of physicians to standard practice and to improve the anesthetic system process.

Survey of anesthesia-related mortality in France

Background and objectives To understand the mechanisms related to both the onset and correction of severe anaemia after orthopaedic surgery, we analysed all the full blood counts (FBCs) for patients on one orthopaedic ward during a one-year period in an academic hospital. Methods FBCs were screened and the medical records of those patients for whom a postoperative haemoglobin (Hb) concentration below 8 g/dL was recorded at least once were reviewed. The onset of postoperative anaemia was determined by calculating the various time intervals delineated by surgery, the time at which the transfusion threshold was reached and the time at which the lowest Hb level (nadir) and transfusion (if any) occurred. Results A total of 6573 FBCs drawn from 1255 patients were screened. The medical records of 74 consecutive patients with at least one Hb value  Conclusions Delayed transfusion (defined as > 12 hours between the time at which the transfusion threshold was reached and actual transfusion) was observed in 57% of severely anaemic patients after orthopaedic surgery.

André Lienhart

Papers

Survey of anesthesia-related mortality in France

Hospital audit of delayed transfusion after orthopaedic surgery.