Lars S. Rasmussen

Randomized evaluation of pulse oximetry in 20,802 patients. II: Perioperative events and postoperative complications

BackgroundThe authors describe the effect of pulse oximetry monitoring on the frequency of unanticipated perl-operative events, changes In patient care, and the rate of postoperative complications in a prospective randomized study. MethodsThe study Included 20,802 surgical patients in Denmark randomly assigned to be monitored or not with pulse oximetry In the operating room (OR) and postanesthesla care unit (PACU). ResultsDuring anesthesia and in the PACU, significantly more patients in the oximetry group had at least one respiratory event than did the control patients. This was the result of a 19-fold Increase in the incidence of diagnosed hypoxemia in the oximetry group than in the control group in both the OR and PACU (P < 0.00001). In the OR, cardiovascular events were observed In a similar number of patients in both groups, except myocardial ischemia (as denned by angina or ST-seg-ment depression), which was detected in 12 patients in the oximetry group and In 26 patients in the control group (P < 0.03). Several changes in PACU care were observed in association with the use of pulse oximetry. These Included higher flow rate of supplemental oxygen (P < 0.00001), Increased use of supplemental oxygen at discharge (P < 0.00001), and increased use of naloxone (P < 0.02). The rate of changes in patient care as a consequence of the oximetry monitoring Increased as the American Society of Anesthesiologists physical status worsened (P < 0.00001). One or more postoperative complications occurred in 10% of the patients in the oximetry group and in 9.4% in the control group (difference not significant). The two groups did not differ significantly in cardiovascular, respiratory, neurologic, or Infectious complications. The duration of hospital stay was a median of 5 days in both groups (difference not significant). An equal number of in-hospital deaths were registered in the two groups. Questionnaires, completed by the anesthesiologists at the five partlc

Randomized evaluation of pulse oximetry in 20,802 patients: I. Design, demography, pulse oximetry failure rate, and overall complication rate.

BackgroundAlthough pulse oximetry is currently In widespread use, there are few data documenting Improvement in patient outcome as a result of the use of oximetry. The authors describe the study design, patient demographic findings, data validation, pulse oximetry failure rate, and overall postoperative complication rates in the first large prospective randomized multicenter clinical trial on perloperative pulse oximetry monitoring. Methods;In five Danish hospitals, by random assignment, monitoring did or did not include pulse oximetry for patients 18 yr of age and older, whether scheduled for elective or emergency operations, or for regional or general anesthesia, except during cardiac and neurosurgical procedures. Operational definitions were established for perioperative events and postoperative complications. The data were collected preoperatively, during anesthesia, in the postanesthesia care unit, and until the day of discharge from the hospital or the seventh postoperative day. ResultsOf 20,802 patients, 10,312 were assigned to the oximetry group and 10,490, to the control group. In general, the demographic data, patient factors, and anesthetic agents used were distributed evenly. A slight intergroup difference was found in the distribution of age, duration of surgery, some types of surgery, and some types of anesthesia. The total failure rate of the oximetry was 2.5%, but it increased to 7.2% in patients with American Society of Anesthesiologists physical status 4 (P < 0.00001). In 14.9% of the patients, one or more events occurred in the operating room and 13.5% in the postanesthesia care unit. The overall postoperative complication rate was 9.7%. The total rates of cardiovascular and respiratory complications were 2.78% and 3.50%, respectively. Within the

Apolipoprotein E Genotype and Cognitive Dysfunction after Noncardiac Surgery

Background:Apolipoprotein E is important in recovery after neuronal damage. The &egr;4 allele of the apolipoprotein E gene has been shown as a risk factor for Alzheimer disease, poor outcome after cerebral injury, and accelerated cognitive decline with normal aging. The authors hypothesized that patients with the &egr;4 allele would have an increased risk of postoperative cognitive dysfunction (POCD) after noncardiac surgery. Methods:In a multicenter study, a total of 976 patients aged 40 yr and older undergoing noncardiac surgery were tested preoperatively and 1 week and 3 months after surgery with a neuropsychological test battery comprising seven subtests. POCD was defined as a decline in test performance of more than 2 SD from the expected. Apolipoprotein E genotypes were determined by blood sample analysis at a central laboratory. Multivariate logistic regression analysis with POCD as the dependent variable assessed presence of the &egr;4 allele (yes/no) and other possible risk factors. Results:The &egr;4 allele was found in 272 patients. One week after surgery, the incidence of POCD was 11.7% in patients with the &egr;4 allele and 9.9% in patients without the &egr;4 allele (P = 0.41). Three months later, POCD was found in 10.3% of patients with the &egr;4 allele and in 8.4% of patients without the &egr;4 allele (P = 0.40). Multivariate logistic regression analysis did not identify the &egr;4 allele as a risk factor at 1 week (P = 0.33) or 3 months (P = 0.57). Conclusions:The authors were unable to show a significant association between apolipoprotein E genotype and POCD, but statistical power was limited because of a lower incidence of POCD than expected.

Infection Risk with Nitrofurazone-Impregnated Urinary Catheters in Trauma Patients: A Randomized Trial

Context Indwelling urinary catheters increase risk for bacteriuria and clinically significant urinary tract infection. Contribution In this randomized trial, trauma patients who received a catheter impregnated with nitrofurazone were less likely to have bacteriuria and funguria than were those who received a standard silicone catheter. They were also less likely to need a change in antibiotic or addition of new antibiotics. Caution Data on outcomes were missing for many patients. Implication By reducing the incidence of bacteriuria and funguria, nitrofurazone-impregnated urinary catheters appear to reduce the need to change or prescribe new antimicrobial therapy in patients who require indwelling catheters. The Editors Urinary tract infection (UTI) is one of the most common nosocomial infections in hospitalized patients and is most often associated with an indwelling catheter (1). The leading risk factor for bacteriuria is the duration of catheterization: With each day of catheterization, the prevalence of bacteriuria increases 3% to 10% (2). Trauma patients are prone to infectious complications (3, 4), in part as a result of invasive devices in supportive therapy. Urinary catheters are often needed in the trauma care setting, and UTI accounts for 24% of nosocomial infections (5). Urinary tract infection is the focus for sepsis in 6% to 8% of injured patients (6), and sepsis is associated with increased mortality (7). The best preventive measure for catheter-associated UTI is to minimize the use of indwelling catheters and to remove catheters as soon as possible. However, other approaches to reduce catheter-associated UTI are required. One possibility is to incorporate antibacterial agents, such as nitrofurazone, in the catheter material. Doing so may prevent migration of bacteria, colonization of the catheter, and formation of biofilm. Like nitrofurantoin, nitrofurazone is a nitrofuran and has been used for more than 50 years without any sign of microbial resistance (8, 9). In vitro studies have shown that nitrofurazone-impregnated catheters inhibited the growth of 75% of common urinary bacterial isolates (10) and of several multidrug-resistant isolates (11). We designed a randomized, double-blind, controlled clinical trial to test the hypothesis that nitrofurazone-impregnated urinary catheters could reduce the incidence of catheter-associated UTI in adult trauma patients compared with standard silicone catheters. Methods Design We conducted a randomized, double-blind, controlled trial comparing a nitrofurazone-impregnated urinary catheter (Releen NF, Coloplast A/S, Humlebaek, Denmark) with a standard silicone urinary catheter (Simpla All Silicone, Coloplast A/S) in trauma patients. Setting and Participants During a 24-month period (July 2003 to August 2005), we included all consecutive adult (age 18 years) trauma patients who needed a urinary catheter and were admitted directly from the accident scene to the Trauma Center in Copenhagen, Denmark. Exclusion criteria were HIV infection; preinjury treatment with corticosteroids; pregnancy; primary burn injury; and unattainable signed informed consent. The Trauma Center in Copenhagen is a level 1 trauma center at a tertiary university hospital. After the trauma resuscitation phase, patients were transferred to an intensive care unit or a surgical ward. On arrival, prophylactic antibiotics were given according to the site and type of injury. Antibiotics were not given for minor injuries. For closed injuries, intravenous cefuroxime, 1.5 g 3 times daily, was given for up to 3 days; for open injuries, intravenous ceftriaxone, 2 g twice a day for up to 3 days, combined with metronidazole, 500 mg 3 times daily, was given. This regimen was continued regardless of which ward or intensive care unit the patient was admitted to. The local ethics committee and the Danish Data Protection Agency approved the study, and written informed consent was obtained from the patients or next of kin. The study was performed in accordance with the 1975 Declaration of Helsinki, as revised in 1983. Randomization and Interventions The randomization list was computer-generated, with a block size of 8 (Medstat, version 2.1; ASTRA Group A/S, Albertslund, Denmark), by a biostatistician who was independent of the investigators. The trauma team leader enrolled patients; at enrollment, allocation to treatment groups was concealed. Two nurses from a team of nurses specially trained in the allocation and catheterization procedure performed the allocation by sequentially opening consecutively numbered, sealed randomization envelopes that contained the name of the assigned catheter. Catheterizing nurses were not formally blinded to catheter type, but both study catheters were new in the hospital. Thus, nurses caring for the patients did not know which of the new catheters was the nitrofurazone catheter. Patients were effectively blinded to their catheter assignment because 1) the catheter package was opened outside the patients field of vision; 2) the patients could not see the catheter at the time of insertion because their necks were immobilized (12); and 3) although the catheters differed only in color, patients were not informed of the name or type of the catheter used. All catheterizations were performed according to standard hospital guidelines. The patients genitals were washed with water and soap (Cutan Skin Care System, DEB, Belper, United Kingdom), sterile gloves and aseptic insertion technique were used, sterile antiseptic gel (Instillagel [lidocaine 2%, chlorhexidine 0.25%], Farco-Pharma, Kln, Germany) was inserted into the urethra, and isotonic sodium chloride was used to fill the balloon. Finally, the catheter was connected to a urine bag with an antireflux valve (UnoMeter, Unomedical A/S, Birkeroed, Denmark) forming the closed drainage system. Adhesive tape was used to assess whether the system had remained unbroken. The size of the catheter used was determined by clinical evaluation; catheters were available in sizes 12 to 16 French. Catheters were removed at the treating physicians discretion as soon as permitted by the patients condition. Outcomes and Follow-up The primary outcome variable was the incidence of catheter-associated bacteriuria and funguria (CABF), defined a priori as bacteriuria or funguria with at least 103 colony-forming units (CFU)/mL for at least 1 isolate, regardless of whether the patients experienced symptoms. The primary outcome variable was chosen as a surrogate end point for catheter-associated UTI. In addition, a post hoc analysis was done with CABF defined as at least 105 CFU/mL. A urine sample for culture was taken immediately after catheter insertion and then daily until the catheter was removed. Aseptic 5-mL urine samples were taken by syringe aspiration from the sampling port without violating the closed drainage system. Samples were immediately refrigerated at 4 C and were subsequently transferred to the laboratory as quickly as possible. On arrival in the laboratory, 1 L and 10 L of urine were cultivated on 5% horse blood agar plates and on McCoy agar plates (Statens Serum Institut, Copenhagen, Denmark) for the culture quantitative analysis. The procedure is standard at the laboratory, and the technicians were blinded to the type of catheter used. After incubation at 37 C, the plates were inspected for growth and the number of CFU was calculated. Bacteria and fungi were identified by the automatic ATB Expression using the API identification system (bioMrieux, Marcy ltoile, France). Antibiotic sensitivity testing was performed by using Neo-sensitab (Rosco A/S, Taastrup, Denmark). The microbiologist evaluating the urine cultures was blinded to the type of catheter used. Blinded data were entered into the electronic database at the Department of Clinical Microbiology, and the treating physician was informed of the culture results. Decisions regarding antimicrobial therapy were at the treating physicians discretion. All patients were assessed daily by the investigators to ensure correct catheter assignment in enrolled patients, to ascertain whether enrolled patients still had the study catheter in place, and to determine whether the closed system had remained unbroken. If the closed system had been violated or the study catheter had been removed, results from subsequent urine samples were not included in the final analysis. In addition, demographic characteristics, clinical variables, Injury Severity Score (ISS), and 30-day survival were recorded. The ISS is based on anatomical evaluation of the injury severity and was calculated according to the method of Baker and colleagues, with use of the 1998 update (13). The scores range from 0 (no injury) to 75 (unsurvivable injury), and a value greater than 15 indicates severe injury. It correlates linearly with mortality, morbidity, and length of hospital stay (13, 14). Statistical Analysis We expected 20% of catheterized trauma patients to develop CABF. On the basis of 80% power to detect a 65% reduction in the incidence of CABF in the nitrofurazone group, with a significance level of P less than 0.05 (2-sided), the required sample size was 200 patients. We therefore planned to enroll 212 patients to compensate for dropouts. Data are presented as proportions or medians with interquartile ranges. We compared results by using regression models (log-binomial, log-binomial [negative], log-Poisson approximation to log-binomial), Fisher exact tests, or MannWhitney U tests, as appropriate. For the prespecified primary analysis (per protocol), patients were excluded if 1 of the following criteria was fulfilled: removal of catheter within 24 hours after insertion, failure to obtain a follow-up urine sample after 24 hours, and bacteriuria or funguria (colonization 103 CFU/mL) at admission. To examine the effects of loss to follow-up, we performed an intention-to-treat analysis with a multiple imputation approach un

Rational use of oxygen in medical disease and anesthesia.

PURPOSE OF REVIEWnSupplemental oxygen is often administered during anesthesia and in critical illness to treat hypoxia, but high oxygen concentrations are also given for a number of other reasons such as prevention of surgical site infection (SSI). The decision to use supplemental oxygen is, however, controversial, because of large heterogeneity in the reported results and emerging reports of side-effects. The aim of this article is to review the recent findings regarding benefits and harms of oxygen therapy in anesthesia and acute medical conditions.nnnRECENT FINDINGSnLarge randomized trials have not found significant reductions in SSI with 80% oxygen during and after abdominal surgery and cesarean section. There is no documented benefit of hyperbaric oxygen treatment for acute ischemic stroke, and there is emerging data to suggest increased mortality with normobaric supplemental oxygen for myocardial infarction without heart failure. Survival and neurologic outcome seem to be adversely affected by hyperoxia in patients with return of spontaneous circulation after cardiac arrest.nnnSUMMARYnThe benefits of supplemental oxygen are not yet confirmed, and new findings suggest that potential side-effects should be considered if the inspired oxygen concentration is increased above what is needed to maintain normal arterial oxygen saturation.

Cognitive Functioning after Surgery in Middle-aged and Elderly Danish Twins

Background:Postoperative cognitive dysfunction is common, but it remains unclear whether there are long-term adverse cognitive effects of surgery combined with anesthesia. The authors examined the association between exposure to surgery and level of cognitive functioning in a sample of 8,503 middle-aged and elderly twins. Methods:Results from five cognitive tests were compared in twins exposed to surgery, classified as major, minor, hip and knee replacement, or other, with those of a reference group without surgery using linear regression adjusted for sex and age. Genetic and shared environmental confounding was addressed in intrapair analyses of 87 monozygotic and 124 dizygotic same-sexed twin pairs in whom one had a history of major surgery and the other did not. Results:Statistically significantly lower composite cognitive score was found in twins with at least one major surgery compared with the reference group (mean difference, −0.27; 95% CI, −0.48 to −0.06), corresponding to one tenth of an SD, that is, a negligible effect size. In the intrapair analysis, the surgery-exposed co-twin had the lower cognitive score in 49% (95% CI, 42 to 56%) of the pairs. None of the other groups differed from the reference group except the knee and hip replacement group that tended to have higher cognitive scores (mean difference, 0.35; 95% CI, −0.18 to 0.87). Conclusions:A history of major surgery was associated with a negligibly lower level of cognitive functioning. The supplementary analyses suggest that preoperative cognitive functioning and underlying diseases were more important for cognitive functioning in mid- and late life than surgery and anesthesia.

Inspiratory Oxygen Fraction and Postoperative Complications in Obese Patients A Subgroup Analysis of the PROXI Trial

Background:Obese patients are at a high risk of postoperative complication, including surgical site infection (SSI). Our aim was to evaluate the effect of a high inspiratory oxygen fraction (80%) on SSI and pulmonary complications in obese patients undergoing laparotomy. Methods:This study was a planned analysis of the obese patients (body mass index ≥ 30 kg/m2) recruited in the Danish multicenter, patient- and observer-blinded, PROXI Trial of 1,400 patients undergoing acute or elective laparotomy. Patients were randomized to receive either 80% or 30% oxygen during and for 2 h after surgery. The primary outcome was SSI within 14 days. Secondary outcomes were atelectasis, pneumonia, and respiratory failure. Results:Two hundred thirteen patients had a body mass index ≥ 30 kg/m2. The median (5–95% range) body mass index was 34 kg/m2 (30–44) and 33 kg/m2 (30–41) in patients allocated to the 80% and 30% oxygen group. SSI occurred in 32 of 102 (31%) versus 29 of 111 (26%) patients given 80% and 30% oxygen, respectively (odds ratio, 1.29; 95% CI, 0.71–2.34; P = 0.40). In addition, the incidence of pulmonary complications was not significantly different, with atelectasis occurring in 9% versus 6%, pneumonia in 6% versus 5%, and respiratory failure in 8% versus 5% in patients given 80% and 30% oxygen, respectively. Conclusion:Administration of 80% oxygen, compared with 30% oxygen, did not reduce the frequency of SSI in obese patients. Moreover, no significant association was found between oxygen fraction and the risk of pulmonary complications.

How does extracerebral trauma affect the clinical value of S100B measurements

Background Protein S100B has proven to be a useful biomarker for cerebral damage. The predictive ability of S100B may, however, be affected by extracerebral injuries. The aim of this study was to investigate serum levels of S100B in patients with either isolated head injury (IHI), multi trauma with head injury (MTHI), or no head injury (NHI). The primary aim was to assess if a significant difference in serum levels of S100B could be found between IHI and MTHI patients. Methods Patients (233) were primarily admitted to the trauma centre. Serum samples were drawn on admission and 6u2005h after trauma and then stored at −80°C until analysed. Variables included Abbreviated Injury Scale (AIS) for head trauma, Injury Severity Score (ISS) and 30-day survival. Results Two patients could not be classified. IHI occurred in 28, MTHI in 102 and NHI was found in 101. The median S100B concentrations on arrival were 0.47, 1.68 and 0.49u2005μg/l, respectively (p<0.0001). The corresponding values at 6u2005h were 0.14, 0.31 and 0.15u2005μg/l, respectively (p<0.0001). S100B was significantly higher in patients with MTHI than in patients with IHI at both time points (p values 0.0005 and 0.01). There was no significant difference in S100B between patients having IHI and patients with NHI (p=0.81 and p=0.67). Conclusions High serum levels of S100B were found early after trauma. The highest concentrations of S100B were found in patients with multi trauma. This suggests that S100B serum concentrations are significantly affected by extracerebral injuries.

Distributing personal resuscitation manikins in an untrained population: how well are basic life support skills acquired?

Background Self-instruction with a DVD and a simple personal manikin is an effective alternative to traditional basic life support (BLS) courses. Objective To evaluate the effect of distributing DVD training kits to untrained laypersons. BLS skills were compared according to 2005 guidelines for resuscitation after 3.5u2005months with those obtained in untrained laypersons who completed the same course with instructor facilitation. Methods BLS skills of 55 untrained laypersons were assessed using the Laerdal ResusciAnne and PC Skill Reporting System in a 3u2005min test and a total score (12–48 points) was calculated. The participants received a DVD training kit without instructions. The test was repeated after 3.5u2005months. Data were compared with data from a previous published study where participants completed the same course in groups with instructor facilitation. Results There was no statistically significant difference in the total score after 3.5u2005months. The ‘DVD—self-instructor’ group obtained 33 (29–37) points and the ‘DVD—with instructor’ group obtained 34 (32–37) points, p=0.16. The ‘DVD—with instructor’ group performed significantly better in checking responsiveness and had a significantly shorter ‘total hands-off time’ (s) (85 (76–94) vs 96 (82–120), p=0.002) and delay until first compression or ventilation group (29u2005s (17–40) vs 33u2005s (22–48), p=0.04). Conclusions Since no significant difference in total BLS score was found after 3.5u2005months between untrained laypersons who either completed a DVD-based BLS course in groups with instructor facilitation or received the same DVD training kit without instruction, the latter seems more efficient.

18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT scans as diagnostic tools in focal congenital hyperinsulinism: a blinded evaluation

PurposeFocal congenital hyperinsulinism (CHI) is curable by surgery, which is why identification of the focal lesion is crucial. We aimed to determine the use of 18F–fluoro-dihydroxyphenylalanine (18F-DOPA) PET/CT vs. 68Ga-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic-acid-1-Nal3-octreotide (68Ga-DOTANOC) PET/CT as diagnostic tools in focal CHI.MethodsPET/CT scans of children with CHI admitted to Odense University Hospital between August 2005 and June 2016 were retrospectively evaluated visually and by their maximal standardized uptake values (SUVmax) by two independent examiners, blinded for clinical, surgical and pathological data. Pancreatic histology was used as the gold standard. For patients without surgery, the genetic profile served as the gold standard.ResultsFifty-five CHI patients were examined by PET/CT (18F-DOPA nxa0=xa053, 68Ga-DOTANOC nxa0=xa018). Surgery was performed in 34 patients, no surgery in 21 patients. Fifty-one patients had a classifiable outcome, either by histology (nxa0=xa033, 22 focal lesions, 11 non-focal) or by genetics (nxa0=xa018, all non-focal). The predictive performance of 18F-DOPA PET/CT to identify focal CHI was identical by visual- and cut-off-based evaluation: sensitivity (95% CI) of 1 (0.85–1); specificity of 0.96 (0.82–0.99). The optimal 18F-DOPA PET SUVmax ratio cut-off was 1.44 and the optimal 68Ga-DOTANOC PET SUVmax cut-off was 6.77xa0g/ml. The area under the receiver operating curve was 0.98 (0.93–1) for 18F-DOPA PET vs. 0.71 (0.43–0.95) for 68Ga-DOTANOC PET (pxa0<xa00.03). In patients subjected to surgery, localization of the focal lesion was correct in 91%, and 100%, by 18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT, respectively.Conclusion18F-DOPA PET/CT was excellent in predicting focal CHI and superior compared to 68Ga-DOTANOC PET/CT. Further use of 68GA-DOTANOC PET/CT in predicting focal CHI is discouraged.