Perioperative Immunosuppressive Factors during Cancer Surgery: An Updated Review.

Surgical excision of the primary tumor represents the most frequent and curative procedure for solid malignancies. Compelling evidence suggests that, despite its beneficial effects, surgery may impair immunosurveillance by triggering an immunosuppressive inflammatory stress response and favor recurrence by stimulating minimal residual disease. In addition, many factors interfere with the immune effectors before and after cancer procedures, such as malnutrition, anemia, or subsequent transfusion. Thus, the perioperative period plays a key role in determining oncological outcomes and represents a short phase to circumvent anesthetic and surgical deleterious factors by supporting the immune system through the use of synergistic pharmacological and non-pharmacological approaches. In line with this, accumulating studies indicate that anesthetic agents could drive both protumor or antitumor signaling pathways during or after cancer surgery. While preclinical investigations focusing on anesthetics' impact on the behavior of cancer cells are quite convincing, limited clinical trials studying the consequences on survival and recurrences remain inconclusive. Herein, we highlight the main factors occurring during the perioperative period of cancer surgery and their potential impact on immunomodulation and cancer progression. We also discuss patient management prior to and during surgery, taking into consideration the latest advances in the literature.

Long-term Survival after Volatile or Propofol General Anesthesia for Bladder Cancer Surgery: A Retrospective National Registry Cohort Study.

BACKGROUND: Prospective interventional trials and retrospective observational analyses provide conflicting evidence regarding the relationship between propofol versus inhaled volatile general anesthesia and long-term survival after cancer surgery. Specifically, bladder cancer surgery lacks prospective clinical trial evidence. METHODS: Data on bladder cancer surgery performed under general anesthesia between 2014 and 2021 from the National Quality Registry for Urinary Tract and Bladder Cancer and the Swedish Perioperative Registry were record-linked. Overall survival was compared between patients receiving propofol or inhaled volatile for anesthesia maintenance. The minimum clinically important difference was defined as a 5-percentage point difference in 5-yr survival. RESULTS: Of 7,571 subjects, 4,519 (59.7%) received an inhaled volatile anesthetic, and 3,052 (40.3%) received propofol for general anesthesia maintenance. The two groups were quite similar in most respects but differed in American Society of Anesthesiologists Physical Status and tumor stage. Propensity score matching was used to address treatment bias. Survival did not differ during follow-up (median, 45 months [interquartile range, 33 to 62 months]) in the full unmatched cohort nor after 1:1 propensity score matching (3,052 matched pairs). The Kaplan-Meier adjusted 5-yr survival rates in the matched cohort were 898 of 3,052, 67.5% (65.6 to 69.3%) for propofol and 852 of 3,052, 68.5% (66.7 to 70.4%) for inhaled volatile general anesthesia, respectively (hazard ratio, 1.05 [95% CI, 0.96 to 1.15]; P = 0.332). A sensitivity analysis restricted to 1,766 propensity score-matched pairs of patients who received only one general anesthetic during the study period did not demonstrate a difference in survival; Kaplan-Meier adjusted 5-yr survival rates were 521 of 1,766, 67.1% (64.7 to 69.7%) and 482 of 1,766, 68.9% (66.5 to 71.4%) for propofol and inhaled volatile general anesthesia, respectively (hazard ratio, 1.09 [95% CI, 0.97 to 1.23]; P = 0.139). CONCLUSIONS: Among patients undergoing bladder cancer surgery under general anesthesia, there was no statistically significant difference in long-term overall survival associated with the choice of propofol or an inhaled volatile maintenance.

Impact of general anaesthesia on breast cancer survival: a 5-year follow up of a pragmatic, randomised, controlled trial, the CAN-study, comparing propofol and sevoflurane.

Background: Anaesthesia may impact long-term cancer survival. In the Cancer and Anaesthesia study, we hypothesised that the hypnotic drug propofol will have an advantage of at least five percentage points in five-year survival over the inhalational anaesthetic sevoflurane for breast cancer surgery. Methods: From 2118 eligible breast cancer patients scheduled for primary curable, invasive breast cancer surgery, 1764 were recruited after ethical approval and individual informed consent to this open label, single-blind, randomised trial at four county- and three university hospitals in Sweden and one Chinese university hospital. Of surveyed patients, 354 were excluded, mainly due to refusal to participate. Patients were randomised by computer at the monitoring organisation to general anaesthesia maintenance with either intravenous propofol or inhaled sevoflurane in a 1:1 ratio in permuted blocks. Data related to anaesthesia, surgery, oncology, and demographics were registered. The primary endpoint was five-year overall survival. Data are presented as Kaplan-Meier survival curves and Hazard Ratios based on Cox univariable regression analyses by both intention-to-treat and per-protocol. EudraCT, 2013-002380-25 and ClinicalTrials.gov, NCT01975064. Findings: Of 1764 patients, included from December 3, 2013, to September 29, 2017, 1670 remained for analysis. The numbers who survived at least five years were 773/841 (91.9% (95% CI 90.1-93.8)) in the propofol group and 764/829 (92.2% (90.3-94.0)) in the sevoflurane group, (HR 1.03 (0.73-1.44); P = 0.875); the corresponding results in the per-protocol-analysis were: 733/798 (91.9% (90.0-93.8)) and 653/710 (92.0% (90.0-94.0)) (HR = 1.01 (0.71-1.44); P = 0.955). Survival after a median follow-up of 76.7 months did not indicate any difference between the groups (HR 0.97, 0.72-1.29; P = 0.829, log rank test). Interpretation: No difference in overall survival was found between general anaesthesia with propofol or sevoflurane for breast cancer surgery. Funding: Swedish Research Council; Uppsala-Örebro Regional Research Council; Västmanland Regional Research Fund; Västmanland Cancer Foundation; Stig and Ragna Gohrton Foundation; Birgit and Henry Knutsson Foundation.

Number of transurethral procedures after non-muscle-invasive bladder cancer and survival in causes other than bladder cancer.

BACKGROUND: Previous research has associated repeated transurethral procedures after a diagnosis of non-muscle invasive bladder cancer (NMIBC) with increased risk of death of causes other than bladder cancer. AIM: We investigated the overall and disease-specific risk of death in patients with NMIBC compared to a background population sample. METHODS: We utilized the database BladderBaSe 2.0 containing tumor-specific, health-related and socio-demographic information for 38,547 patients with NMIBC not primarily treated with radical cystectomy and 192,733 individuals in a comparison cohort, matched on age, gender, and county of residence. The cohorts were compared using Kaplan-Meier curves and Hazard ratios (HR) from a Cox regression models. In the NMIBC cohort, we analyzed the association between number of transurethral procedures and death conditioned on surviving two or five years. RESULTS: Overall survival and survival from causes other than bladder cancer estimated with Kaplan-Meier curves was 9.3% (95% confidence interval (CI) (8.6%-10.0%)) and 1.4% (95% CI 0.7%-2.1%) lower respectively for the NMIBC cohort compared to the comparison cohort at ten years. In a Cox model adjusted for prognostic group, educational level and comorbidity, the HR was 1.03 (95% CI 1.01-1.05) for death from causes other than bladder cancer comparing the NMIBC cohort to the comparison cohort. Among the NMIBC patients, there was no discernible association between number of transurethral procedures and deaths of causes other than bladder cancer after adjustment. The number of procedures were, however, associated with risk of dying from bladder cancer HR 3.56 (95% CI 3.43-3.68) for four or more resections versus one within two years of follow-up. CONCLUSION: The results indicate that repeated diagnostic or therapeutic transurethral procedures under follow-up do not increase of risk dying from causes other than bladder cancer. The modestly raised risk for NMIBC patients dying from causes other than bladder cancer is likely explained by residual confounding.

Volatile versus Propofol General Anesthesia and Long-term Survival after Breast Cancer Surgery: A National Registry Retrospective Cohort Study.

BACKGROUND: Several retrospective studies using administrative or single-center data have failed to show any difference between general anesthesia using propofol versus inhaled volatiles on long-term survival after breast cancer surgery. Although randomized controlled trials are ongoing, validated data from national clinical registries may advance the reliability of existing knowledge. METHODS: Data on breast cancer surgery performed under general anesthesia between 2013 and 2019 from the Swedish PeriOperative Registry and the National Quality Registry for Breast Cancer were record-linked. Overall survival was compared between patients receiving propofol and patients receiving inhaled volatile for anesthesia maintenance. RESULTS: Of 18,674 subjects, 13,873 patients (74.3%) received propofol and 4,801 (25.7%) received an inhaled volatile for general anesthesia maintenance. The two cohorts differed in most respects. Patients receiving inhaled volatile were older (67 yr vs. 65 yr), sicker (888 [19.0%] American Society of Anesthesiologists status 3 to 5 vs. 1,742 [12.8%]), and the breast cancer to be more advanced. Median follow-up was 33 months (interquartile range, 19 to 48). In the full, unmatched cohort, there was a statistically significantly higher overall survival among patients receiving propofol (13,489 of 13,873 [97.2%]) versus inhaled volatile (4,039 of 4,801 [84.1%]; hazard ratio, 0.80; 95% CI, 0.70 to 0.90; P < 0.001). After 1:1 propensity score matching (4,658 matched pairs), there was no statistically significant difference in overall survival (propofol 4,284 of 4,658 [92.0%]) versus inhaled volatile (4,288 of 4,658 [92.1%]; hazard ratio, 0.98; 95% CI, 0.85 to 1.13; P = 0.756). CONCLUSIONS: Among patients undergoing breast cancer surgery under general anesthesia, no association was observed between the choice of propofol or an inhaled volatile maintenance and overall survival.

Is It Definitely Clear That Long-Term Survival after Breast Cancer Surgery Is Not Affected by Anaesthetics?

Retrospective studies indicate that cancer survival may be affected by the anaesthetic technique. Propofol seems to be a better choice than volatile anaesthetics, such as sevoflurane. The first two retrospective studies suggested better long-term survival with propofol, but not for breast cancer. Subsequent retrospective studies from Asia indicated the same. When data from seven Swedish hospitals were analysed, including 6305 breast cancer patients, different analyses gave different results, from a non-significant difference in survival to a remarkably large difference in favour of propofol, an illustration of the innate weakness in the retrospective design. The largest randomised clinical trial, registered on clinicaltrial.gov, with survival as an outcome is the Cancer and Anesthesia study. Patients are here randomised to propofol or sevoflurane. The inclusion of patients with breast cancer was completed in autumn 2017. Delayed by the pandemic, one-year survival data for the cohort were presented in November 2020. Due to the extremely good short-term survival for breast cancer, one-year survival is of less interest for this disease. As the inclusions took almost five years, there was also a trend to observe. Unsurprisingly, no difference was found in one-year survival between the two groups, and the trend indicated no difference either.

Survival after primary breast cancer surgery following propofol or sevoflurane general anesthesia-A retrospective, multicenter, database analysis of 6305 Swedish patients.

BACKGROUND: Retrospective studies indicate that the choice of anesthetic can affect long-term cancer survival. Propofol seems to have an advantage over sevoflurane. However, this is questioned for breast cancer. We gathered a large cohort of breast cancer surgery patients from seven Swedish hospitals and hypothesized that general anesthesia with propofol would be superior to sevoflurane anesthesia regarding long-term breast cancer survival. METHODS: We identified all patients who were anaesthetized for breast cancer surgery between 2006 and 2012. The patients were matched to the Swedish Breast Cancer Quality Register, to retrieve tumor characteristics, prognostic factors, and adjuvant treatment as well as date of death. Overall survival between patients undergoing sevoflurane and propofol anesthesia was analyzed with different statistical approaches: (a) multiple Cox regression models adjusted for demographic, oncological, and multiple control variables, (b) propensity score matching on the same variables, but also including the participating centers as a cofactor in a separate analysis. RESULTS: The database analysis identified 6305 patients. The 5-year survival rates were 91.0% and 81.8% for the propofol and sevoflurane group, respectively, in the final model (P = .126). Depending on the statistical adjustment method used, different results were obtained, from a non-significant to a "proposed" and even a "determined" difference in survival that favored propofol, with a maximum of 9.2 percentage points higher survival rate at 5 years (hazard ratio 1.46, 95% CI 1.10-1.95). CONCLUSIONS: It seems that propofol may have a survival advantage compared with sevoflurane among breast cancer patients, but the inherent weaknesses of retrospective analyses were made apparent.

Rationale and Design of the CAN Study: an RCT of Survival after Propofol- or Sevoflurane-based Anesthesia for Cancer Surgery.

BACKGROUND: Based on animal data only, some clinicians have adopted propofol-based anesthesia for cancer surgery with the aim of increased survival. OBJECTIVE: Our objective is to verify or refute the hypothesis that survival increases after cancer surgery with propofol compared with sevoflurane for anesthesia maintenance. This aim deserves a large-scale randomized study. The primary hypothesis is an absolute increase of minimum 5%-units in 1- and 5-year survival with propofol- based anesthesia for breast or colorectal cancer after radical surgery, compared with sevoflurane-based anesthesia. METHOD: Ethics and medical agency approvals were received and pre-study registrations at clinicaltrial.gov and EudraCT were made for our now ongoing prospective, randomized, open-label, multicenter study. A power analysis based on a retrospective study, including a safety margin for drop outs, resulted in a total requirement of 8,000 patients. The initial inclusion period constituted a feasibility phase with an emphasis on the functionality of the infrastructure at the contributing centers and at the monitoring organization, as well as on protocol adherence. CONCLUSION: The infrastructure and organization work smoothly at the different contributing centers. Protocol adherence is good, and the monitors are satisfied. We expect this trial to be able to either verify or refute that propofol is better than sevoflurane for cancer surgery.

Positive End-expiratory Pressure and Postoperative Atelectasis: A Randomized Controlled Trial.

BACKGROUND: Positive end-expiratory pressure (PEEP) increases lung volume and protects against alveolar collapse during anesthesia. During emergence, safety preoxygenation preparatory to extubation makes the lung susceptible to gas absorption and alveolar collapse, especially in dependent regions being kept open by PEEP. We hypothesized that withdrawing PEEP before starting emergence preoxygenation would limit postoperative atelectasis formation. METHODS: This was a randomized controlled evaluator-blinded trial in 30 healthy patients undergoing nonabdominal surgery under general anesthesia and mechanical ventilation with PEEP 7 or 9 cm H2O depending on body mass index. A computed tomography scan at the end of surgery assessed baseline atelectasis. The study subjects were thereafter allocated to either maintained PEEP (n = 16) or zero PEEP (n = 14) during emergence preoxygenation. The primary outcome was change in atelectasis area as evaluated by a second computed tomography scan 30 min after extubation. Oxygenation was assessed by arterial blood gases. RESULTS: Baseline atelectasis was small and increased modestly during awakening, with no statistically significant difference between groups. With PEEP applied during awakening, the increase in atelectasis area was median (range) 1.6 (-1.1 to 12.3) cm and without PEEP 2.3 (-1.6 to 7.8) cm. The difference was 0.7 cm (95% CI, -0.8 to 2.9 cm; P = 0.400). Postoperative atelectasis for all patients was median 5.2 cm (95% CI, 4.3 to 5.7 cm), corresponding to median 2.5% of the total lung area (95% CI, 2.0 to 3.0%). Postoperative oxygenation was unchanged in both groups when compared to oxygenation in the preoperative awake state. CONCLUSIONS: Withdrawing PEEP before emergence preoxygenation does not reduce atelectasis formation after nonabdominal surgery. Despite using 100% oxygen during awakening, postoperative atelectasis is small and does not affect oxygenation, possibly conditional on an open lung during anesthesia, as achieved by intraoperative PEEP.

Positive End-expiratory Pressure Alone Minimizes Atelectasis Formation in Nonabdominal Surgery: A Randomized Controlled Trial.

BACKGROUND: Various methods for protective ventilation are increasingly being recommended for patients undergoing general anesthesia. However, the importance of each individual component is still unclear. In particular, the perioperative use of positive end-expiratory pressure (PEEP) remains controversial. The authors tested the hypothesis that PEEP alone would be sufficient to limit atelectasis formation during nonabdominal surgery. METHODS: This was a randomized controlled evaluator-blinded study. Twenty-four healthy patients undergoing general anesthesia were randomized to receive either mechanical ventilation with PEEP 7 or 9 cm H2O depending on body mass index (n = 12) or zero PEEP (n = 12). No recruitment maneuvers were used. The primary outcome was atelectasis area as studied by computed tomography in a transverse scan near the diaphragm, at the end of surgery, before emergence. Oxygenation was evaluated by measuring blood gases and calculating the ratio of arterial oxygen partial pressure to inspired oxygen fraction (PaO2/FIO2 ratio). RESULTS: At the end of surgery, the median (range) atelectasis area, expressed as percentage of the total lung area, was 1.8 (0.3 to 9.9) in the PEEP group and 4.6 (1.0 to 10.2) in the zero PEEP group. The difference in medians was 2.8% (95% CI, 1.7 to 5.7%; P = 0.002). Oxygenation and carbon dioxide elimination were maintained in the PEEP group, but both deteriorated in the zero PEEP group. CONCLUSIONS: During nonabdominal surgery, adequate PEEP is sufficient to minimize atelectasis in healthy lungs and thereby maintain oxygenation. Thus, routine recruitment maneuvers seem unnecessary, and the authors suggest that they should only be utilized when clearly indicated. VISUAL ABSTRACT: An online visual overview is available for this article at http://links.lww.com/ALN/B728.

Minimizing atelectasis formation during general anaesthesia-oxygen washout is a non-essential supplement to PEEP.

BACKGROUND: Following preoxygenation and induction of anaesthesia, most patients develop atelectasis. We hypothesized that an immediate restoration to a low oxygen level in the alveoli would prevent atelectasis formation and improve oxygenation during the ensuing anaesthesia. METHODS: We randomly assigned 24 patients to either a control group (n = 12) or an intervention group (n = 12) receiving an oxygen washout procedure directly after intubation. Both groups were, depending on body mass index, ventilated with a positive end-expiratory pressure (PEEP) of 6-8 cmH2O during surgery. The atelectasis area was studied by computed tomography before emergence. Oxygenation levels were evaluated by measuring blood gases and calculating estimated venous admixture (EVA). RESULTS: The atelectasis areas expressed as percentages of the total lung area were 2.0 (1.5-2.7) (median [interquartile range]) and 1.8 (1.4-3.3) in the intervention and control groups, respectively. The difference was non-significant, and also oxygenation was similar between the two groups. Compared to oxygenation before the start of anaesthesia, oxygenation at the end of surgery was improved in the intervention group, mean (SD) EVA from 7.6% (6.6%) to 3.9% (2.9%) (P = .019) and preserved in the control group, mean (SD) EVA from 5.0% (5.3%) to 5.6% (7.1%) (P = .59). CONCLUSION: Although the oxygen washout restored a low pulmonary oxygen level within minutes, it did not further reduce atelectasis size. Both study groups had small atelectasis and good oxygenation. These results suggest that a moderate PEEP alone is sufficient to minimize atelectasis and maintain oxygenation in healthy patients.

Post-tonsillectomy pain after using bipolar diathermy scissors or the harmonic scalpel: a randomised blinded study.

OBJECTIVE: To compare the postoperative pain following bipolar diathermy scissors tonsillectomy (higher temperature dissection) with harmonic scalpel tonsillectomy (lower temperature dissection). METHODS: Sixty patients aged 7-40 years planned for tonsillectomy with no other concurrent surgery were randomised to either bipolar diathermy scissors or harmonic scalpel as surgical technique. Blinded to the surgical technique, the patients recorded their pain scores (VAS, 0-10) at awakening and the worst pain level of the day in the postoperative period. All intake of pain medication was also recorded. RESULTS: No statistically significant differences were found between the two groups regarding postoperative pain levels or consumption of pain medication. CONCLUSION: Usage of the harmonic scalpel does not render less postoperative pain following tonsillectomy when compared with usage of the bipolar diathermy scissors.

Improved quality and efficiency after the introduction of physician-led team triage in an emergency department.

BACKGROUND: Overcrowding in the emergency department (ED) may negatively affect patient outcomes, so different triage models have been introduced to improve performance. Physician-led team triage obtains better results than other triage models. We compared efficiency and quality measures before and after reorganization of the triage model in the ED at our county hospital. MATERIALS AND METHODS: We retrospectively compared two study periods with different triage models: nurse triage in 2008 (baseline) and physician-led team triage in 2012 (follow-up). Physician-led team triage was in use during day-time and early evenings on weekdays. Data were collected from electronic medical charts and the National Mortality Register. RESULTS: We included 20,073 attendances in 2008 and 23,765 in 2012. The time from registration to physician presentation decreased from 80 to 33 min (P < 0.001), and the length of stay decreased from 219 to 185 min (P < 0.001) from 2008 to 2012, respectively. All of the quality variables differed significantly between the two periods, with better results in 2012. The odds ratio for patients who left before being seen or before treatment was completed was 0.62 (95% confidence interval 0.54-0.72). The corresponding result for unscheduled returns was 0.36 (0.32-0.40), and for the mortality rates within 7 and 30 days 0.72 (0.59-0.88) and 0.84 (0.73-0.97), respectively. The admission rate was 37% at baseline and 32% at follow-up (P < 0.001). CONCLUSION: Physician-led team triage improved the efficiency and quality in EDs.

The patient safety culture as perceived by staff at two different emergency departments before and after introducing a flow-oriented working model with team triage and lean principles: a repeated cross-sectional study.

BACKGROUND: Patient safety is of the utmost importance in health care. The patient safety culture in an institution has great impact on patient safety. To enhance patient safety and to design strategies to reduce medical injuries, there is a current focus on measuring the patient safety culture. The aim of the present study was to describe the patient safety culture in an ED at two different hospitals before and after a Quality improvement (QI) project that was aimed to enhance patient safety. METHODS: A repeated cross-sectional design, using the Hospital Survey On Patient Safety Culture questionnaire before and after a quality improvement project in two emergency departments at a county hospital and a university hospital. The questionnaire was developed to obtain a better understanding of the patient safety culture of an entire hospital or of specific departments. The Swedish version has 51 questions and 15 dimensions. RESULTS: At the county hospital, a difference between baseline and follow-up was observed in three dimensions. For two of these dimensions, Team-work within hospital and Communication openness, a higher score was measured at the follow-up. At the university hospital, a higher score was measured at follow-up for the two dimensions Team-work across hospital units and Team-work within hospital. CONCLUSION: The result showed changes in the self-estimated patient safety culture, mainly regarding team-work and communication openness. Most of the improvements at follow-up were seen by physicians, and mainly at the county hospital.

The choice of anaesthetic--sevoflurane or propofol--and outcome from cancer surgery: a retrospective analysis.

BACKGROUND: Commonly used inhalational hypnotics, such as sevoflurane, are pro-inflammatory, whereas the intravenously administered hypnotic agent propofol is anti-inflammatory and anti-oxidative. A few clinical studies have indicated similar effects in patients. We examined the possible association between patient survival after radical cancer surgery and the use of sevoflurane or propofol anaesthesia. PATIENTS AND METHODS: Demographic, anaesthetic, and surgical data from 2,838 patients registered for surgery for breast, colon, or rectal cancers were included in a database. This was record-linked to regional clinical quality registers. Cumulative 1- and 5-year overall survival rates were assessed using the Kaplan-Meier method, and estimates were compared between patients given propofol (n = 903) or sevoflurane (n = 1,935). In a second step, Cox proportional hazard models were calculated to assess the risk of death adjusted for potential effect modifiers and confounders. RESULTS: Differences in overall 1- and 5-year survival rates for all three sites combined were 4.7% (p = 0.004) and 5.6% (p < 0.001), respectively, in favour of propofol. The 1-year survival for patients operated for colon cancer was almost 10% higher after propofol anaesthesia. However, after adjustment for several confounders, the observed differences were not statistically significant. CONCLUSION: Propofol anaesthesia might be better in surgery for some cancer types, but the retrospective design of this study, with uneven distributions of several confounders, distorted the picture. These uncertainties emphasize the need for a randomized controlled trial.

A ventilation strategy during general anaesthesia to reduce postoperative atelectasis.

BACKGROUND: Atelectasis is common during and after general anaesthesia. We hypothesized that a ventilation strategy, without recruitment manoeuvres, using a combination of continuous positive airway pressure (CPAP) or positive end-expiratory pressure (PEEP) and a reduced end-expiratory oxygen fraction (FETO2) before ending mask ventilation with CPAP after extubation would reduce the area of postoperative atelectasis. METHODS: Thirty patients were randomized into three groups. During induction and emergence, inspiratory oxygen fractions (FIO2) were 1.0 in the control group and 1.0 or 0.8 in the intervention groups. No CPAP/PEEP was used in the control group, whereas CPAP/PEEP of 6 cmH2O was used in the intervention groups. After extubation, FIO2 was set to 0.30 in the intervention groups and CPAP was applied, aiming at FETO2 < 0.30. Atelectasis was studied by computed tomography 25 min postoperatively. RESULTS: The median area of atelectasis was 5.2 cm(2) (range 1.6-12.2 cm(2)) and 8.5 cm(2) (3-23.1 cm(2)) in the groups given FIO2 1.0 with or without CPAP/PEEP, respectively. After correction for body mass index the difference between medians (2.9 cm(2)) was statistically significant (confidence interval 0.2-7.6 cm(2), p = 0.04). In the group given FIO2 0.8, in which seven patients were ex- or current smokers, the median area of atelectasis was 8.2 cm(2) (1.8-14.7 cm(2)). CONCLUSION: Compared with conventional ventilation, after correction for obesity, this ventilation strategy reduced the area of postoperative atelectasis in one of the intervention groups but not in the other group, which included a higher proportion of smokers.

Combined analysis of circulating ß-endorphin with gene polymorphisms in OPRM1, CACNAD2 and ABCB1 reveals correlation with pain, opioid sensitivity and opioid-related side effects.

BACKGROUND: Opioids are associated with wide inter-individual variability in the analgesic response and a narrow therapeutic index. This may be partly explained by the presence of single nucleotide polymorphisms (SNPs) in genes encoding molecular entities involved in opioid metabolism and receptor activation. This paper describes the investigation of SNPs in three genes that have a functional impact on the opioid response: OPRM1, which codes for the µ-opioid receptor; ABCB1 for the ATP-binding cassette B1 transporter enzyme; and the calcium channel complex subunit CACNA2D2. The genotyping was combined with an analysis of plasma levels of the opioid peptide ß-endorphin in 80 well-defined patients with chronic low back pain scheduled for spinal fusion surgery, and with differential sensitivity to the opioid analgesic remifentanil. This patient group was compared with 56 healthy controls. RESULTS: The plasma ß-endorphin levels were significantly higher in controls than in pain patients.A higher incidence of opioid-related side effects and sex differences was found in patients with the minor allele of the ABCB1 gene. Further, a correlation between increased opioid sensitivity and the major CACNA2D2 allele was confirmed. A tendency of a relationship between opioid sensitivity and the minor allele of OPRM1 was also found. CONCLUSIONS: Although the sample cohort in this study was limited to 80 patients it appears that it was possible to observe significant correlations between polymorphism in relevant genes and various items related to pain sensitivity and opioid response. Of particular interest is the new finding of a correlation between increased opioid sensitivity and the major CACNA2D2 allele. These observations may open for improved strategies in the clinical treatment of chronic pain with opioids.