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.

Pre- to postoperative coagulation profile of 307 patients undergoing oesophageal resection with epidural blockade over a 10-year period in a single hospital: implications for the risk of spinal haematoma.

BACKGROUND: Epidural anaesthesia and analgesia are indicated for oesophageal surgery. A rare but serious complication is spinal haematoma, which can occur on insertion, manipulation or withdrawal of catheters. Evidence and guidelines are vague regarding which tests are appropriate and how to interpret their results. We aimed to describe how routine coagulation test results change during oesophagectomy's perioperative course. METHODS: Following ethical approval, we retrospectively identified patients who had undergone oesophagectomy between 2002 and 2012. Blood test results and details of operations, haemorrhage and complications were recorded and analysed with Excel and R. A literature search was conducted using the PubMed terms 'epidural' AND 'coagulation' AND English language. Relevant articles published in 2000 and after were included. RESULTS: Three hundred and seven patients received a thoracic epidural infusion with bupivacaine and morphine while 51 received an intravenous morphine infusion. Tests taken preoperatively and before the planned withdrawal of the epidural catheter demonstrated increases in all three measures: aPTT (activated partial thromboplastin time), PT-INR (prothrombin international normalised ratio) and platelet count (Plc). Postoperative thrombocytopenia was almost non-existent while aPTT or PT-INR was elevated above the reference range in 129/307 patients: aPTT was elevated in 116/307 while PT-INR was elevated in 32/307. This is too small a sample to allow meaningful estimation of risk of spinal haematoma: it may be as high as 2.3%. The literature search returned 275 articles, of which 57 were relevant. Twenty-one concerned the natural history of postoperative coagulation; 16, the incidence of and risk factors for spinal haematoma; and 5, evaluation of specific blood tests. Postoperative coagulation is characterised by thrombocytosis and transient moderately abnormal routine coagulation test results. Viscoelastic tests are not validated in the stable postoperative setting. CONCLUSIONS: Screening for coagulopathy before removal of epidural catheters is of unclear benefit since elevated aPTT and PT-INR are usual and may not indicate hypocoagulation. A thorough clinical assessment is important. We nevertheless recommend caution when being presented with elevated routine tests of coagulation before withdrawing an epidural catheter: viscoelastic haemostatic tests may have a role in testing before withdrawal of epidural catheters but they are so far not validated. Future research should include advanced coagulation analysis as soon as a patient is unfortunate enough to have a spinal haematoma.

Heart rate variability changes in physicians working on night call.

PURPOSE: Adverse effects by night-call duty have become an important occupational health issue. The aim of this study was to investigate whether the heart rate variability (HRV) differed during recovery from day work and night-call duty between distinct physician specialities. METHODS: We studied the impact of a 16-h night-call duty on autonomic balance, measured by HRV, among two physician groups differing with respect to having to deal with life-threatening conditions while on call. Nineteen anaesthesiologists (ANEST) and 16 paediatricians and ear, nose and throat surgeons (PENT) were monitored by ambulatory digital Holter electrocardiogram (ECG). Heart rate variability was analysed between 21:00 and 22:00 after an ordinary workday, on night call and in the evening post-call. Absolute and normalized high-frequency power (HF, HFnu) were the main outcome variables, expressing parasympathetic influence on the heart. RESULTS: ANEST had lower HF power than PENT while on night call and post-daytime work (p < 0.05), but not at post-night call. In the whole group of physicians, HFnu was lower on call and post-daytime work compared with post-night-call duty (p < 0.05). CONCLUSIONS: The physiological recovery after night duty seemed sufficient in terms of HRV patterns for HFnu, reflecting autonomic balance and did not differ between specialities. However, the less dynamic HRV after daytime work and during night-call duty in the ANEST group may indicate a higher physiological stress level. These results may contribute to the improvement of night-call schedules within the health care sector.

Sleep and recovery in physicians on night call: a longitudinal field study.

BACKGROUND: It is well known that physicians' night-call duty may cause impaired performance and adverse effects on subjective health, but there is limited knowledge about effects on sleep duration and recovery time. In recent years occupational stress and impaired well-being among anaesthesiologists have been frequently reported for in the scientific literature. Given their main focus on handling patients with life-threatening conditions, when on call, one might expect sleep and recovery to be negatively affected by work, especially in this specialist group. The aim of the present study was to examine whether a 16-hour night-call schedule allowed for sufficient recovery in anaesthesiologists compared with other physician specialists handling less life-threatening conditions, when on call. METHODS: Sleep, monitored by actigraphy and Karolinska Sleep Diary/Sleepiness Scale on one night after daytime work, one night call, the following first and second nights post-call, and a Saturday night, was compared between 15 anaesthesiologists and 17 paediatricians and ear, nose, and throat surgeons. RESULTS: Recovery patterns over the days after night call did not differ between groups, but between days. Mean night sleep for all physicians was 3 hours when on call, 7 h both nights post-call and Saturday, and 6 h after daytime work (p < 0.001). Scores for mental fatigue and feeling well rested were poorer post-call, but returned to Sunday morning levels after two nights' sleep. CONCLUSIONS: Despite considerable sleep loss during work on night call, and unexpectedly short sleep after ordinary day work, the physicians' self-reports indicate full recovery after two nights' sleep. We conclude that these 16-hour night duties were compatible with a short-term recovery in both physician groups, but the limited sleep duration in general still implies a long-term health concern. These results may contribute to the establishment of safe working hours for night-call duty in physicians and other health-care workers.

The effects of platelet transfusions evaluated using rotational thromboelastometry.

BACKGROUND: In this study, we assessed the immediate effects of platelet transfusion on whole blood coagulation. METHODS: Ten thrombocytopenic patients given a single unit platelet transfusion of 200-300 x 10(9) platelets had their coagulation status assessed before and immediately after transfusion using rotational thromboelastometry. RESULTS: Transfusion increased the median platelet count from 31.5 to 43.5 x 10(9)/L. Clot formation time decreased by 32% (P = 0.005), whereas maximum clot strength increased by 47% (P = 0.005). CONCLUSION: Statistically significant improvements in rotational thromboelastometry-measured parameters were observed in association with a mean increase of 12 x 109/L in platelet count after platelet transfusion in these patients.

Epidural lipomatosis and congenital small spinal canal in spinal anaesthesia: a case report and review of the literature.

INTRODUCTION: Complications after lumbar anaesthesia and epidural blood patch have been described in patients with congenital small spinal canal and increased epidural fat or epidural lipomatosis. These conditions, whether occurring separately or in combination, require magnetic resonance imaging for diagnosis and grading, but their clinical significance is still unclear. CASE PRESENTATION: A 35-year-old Caucasian woman who was undergoing a Caesarean section developed a longstanding L4-L5 unilateral neuropathy after the administration of spinal anaesthesia. There were several attempts to correctly position the needle, one of which resulted in paraesthesia. A magnetic resonance image revealed that the patient's bony spinal canal was congenitally small and had excess epidural fat. The cross-sectional area of the dural sac was then reduced, which left practically no free cerebrospinal fluid space. CONCLUSION: The combination of epidural lipomatosis of varying degrees and congenital small spinal canal has not been previously discussed with spinal anaesthesia. Due to the low cerebrospinal fluid content of the small dural sac, the cauda equina becomes a firm system with a very limited possibility for the nerve roots to move away from the puncture needle when it is inserted into the dural sac. This constitutes risks of technical difficulties and neuropathies with spinal anaesthesia.

Morphine metabolism after major liver surgery.

BACKGROUND: Impaired metabolism of morphine may lead to an increase in sedation and respiratory depression. METHODS: In the present study we investigated morphine pharmacokinetics in patients who had undergone liver resection (n = 15) compared to a control group undergoing colon resection (n = 15). Morphine was administered IV by patient-controlled analgesia. Plasma concentrations of morphine, morphine-6-glucuronide, and morphine-3-glucuronide were measured 2-3 times daily for the first two postoperative days. Pain intensity scores were assessed three times daily and respiratory rate and sedation scores every third hour. RESULTS: There were no differences in morphine requirements 1.1 (0.8-2.5 [median, interquartile range]) mg/h (liver resection) and 1.5 (1.1-1.7) mg/h (colon resection) [P = 0.84]) or in pain intensity scores (P > 0.3) between the groups. Plasma morphine concentrations were higher in patients undergoing liver resection than in the control group (P < 0.01) reflecting a lower rate of morphine metabolism. Plasma morphine concentrations were correlated with the volume of liver resection (P < 0.02). However, plasma concentrations of morphine-6-glucuronide and morphine-3-glucuronide did not differ between the groups (P = 0.62 and P = 0.48, respectively). There was a higher incidence of sedation (P = 0.02), but not respiratory depression (P = 0.48), after liver resection. CONCLUSION: The study demonstrates that plasma concentrations of morphine are higher in patients undergoing liver resection compared with patients undergoing colon resection. Sedation scores were higher in patients undergoing liver resection. Caution is therefore recommended when administering morphine to this patient group.

Thoracic epidural analgesia or intravenous morphine analgesia after thoracoabdominal esophagectomy: a prospective follow-up of 201 patients.

OBJECTIVE: Thoracoabdominal esophagectomy is a major surgical procedure that carries significant postoperative morbidity and mortality. Because the choice of analgesic technique may influence outcome, the impact of thoracic epidural or intravenous analgesia was investigated after esophagectomy. DESIGN: Prospective observational study during January 1996 until January 2002. SETTING: University hospital. PARTICIPANTS: All patients undergoing thoracoabdominal esophagectomy during the 6-year period. INTERVENTIONS: Patients were prospectively monitored during a 6-year period. Duration of surgery, intraoperative blood loss, fluid administration, postoperative intubation time, intensive care unit (ICU) stay, pain relief and related side effects, postoperative complications, hospital stay, and in-hospital and long-term mortality were compared in relation with the analgesic technique. MEASUREMENTS AND MAIN RESULT: Thoracic epidural analgesia with bupivacaine/morphine was used in 166 patients, and intravenous morphine analgesia was used in 35 patients. Postoperative intubation time and ICU stay were similar in both groups. Patients with epidural analgesia experienced less pain. Sedation, respiratory depression, hallucinations, and confusion were more common in the intravenous morphine group. Postoperative weight did not differ between the groups, despite fluid replacement that was higher in the epidural group during the first 24 hours. The in-hospital mortality rate was 0.5%. CONCLUSIONS: No differences in morbidity/mortality rates depending on analgesic treatment were observed in patients undergoing thoracoabdominal esophagectomy. Thoracic epidural analgesia provided better pain relief with fewer opioid-related side effects than intravenous morphine analgesia. However, postoperative epidural analgesia was associated with more technical difficulties.

Apnea and bradypnea in patients receiving epidural bupivacaine-morphine for postoperative pain relief as assessed by a new monitoring method.

STUDY OBJECTIVE: To evaluate postoperative breathing patterns with a new monitoring device in patients given bupivacaine-morphine epidural analgesia. DESIGN: Open explorative study. SETTING: Inpatient anesthesia in a university hospital setting. PATIENTS: 15 ASA physical status I and II patients aged 28 to 87 years and scheduled for major abdominal surgery. INTERVENTIONS: All patients underwent abdominal surgery with epidural anesthesia combined with general anesthesia. Postoperatively, they continued with epidural analgesia consisting of bupivacaine and morphine. On the first postoperative night, the breathing pattern was studied with a new noninvasive monitoring device measuring respiratory frequency and apnea. Arterial blood gas analysis was performed in case of apnea or low respiratory frequency. MEASUREMENTS AND MAIN RESULTS: A total of 84 alarm events were registered in 11 patients. Twenty-one percent (18/84) of the alarms were associated with arterial carbon dioxide tension (PaCO2) levels greater than 48.8 mmHg. Three of the four patients with PaCO2 levels greater than 48.8 mmHg were older than 80 years of age. CONCLUSION: The tested noninvasive monitoring device may detect abnormal respiratory breathing patterns in patients at risk for respiratory depression during epidural analgesia with bupivacaine-morphine.