Hypotension during induction of anaesthesia is neither a reliable nor a useful quality measure for comparison of anaesthetists' performance.

BACKGROUND: Identification of statistically reliable outcomes for comparison among anaesthetists is challenging. Time-weighted intraoperative mean arterial pressure <65 mm Hg (AUC 65 ) is associated with increased odds for myocardial damage. We explored retrospectively whether such hypotension before incision was statistically reliable for peer comparison. METHODS: We retrieved electronic data between 2006 and 2015 at a tertiary care, academic hospital in the USA for patients at risk for myocardial damage (inpatient after surgery, ASA physical status ≥III, ≥50 yr of age, and case duration ≥60 min). We determined the percentage of anaesthetists comparable based on caseload and case-mix. The AUC 65 was compared amongst anaesthetists supervising ≥100 cases involving at-risk patients during the last 12 months. RESULTS: Only 14.1% [95% confidence interval (CI) 13.6-14.5%] of cases involved patients who were 'at risk' during the 10 yr study period. A yearly average of 49 ( sd 6) anaesthetists supervised ≥100 cases of any type, of whom only 52% (95% CI 47.1-56.0%) supervised ≥100 cases involving at-risk patients. Thus, nearly half the anaesthetists would have been excluded from peer comparison. During the last 12 months, there were two outliers among 34 evaluable anaesthetists ( P <0.05, controlling for false discovery). However, their contribution to total hypotension amongst cases for all patients was small, because hypotension was widely distributed (e.g. 80% of hypotension attributable to 61.8% of anaesthetists, 95% CI 59.8-63.7%). There was no relationship between the AUC 65 and propofol induction dose. CONCLUSIONS: The AUC 65 of time-weighted pre-incision hypotension is not a suitable metric for comparing anaesthetists. There were few at-risk patients, half the anaesthetists were not evaluable because of their case-mix and caseload, and hypotension was widely distributed.

Calculating the probability of random sampling for continuous variables in submitted or published randomised controlled trials.

In a previous paper, one of the authors (JBC) used a chi-squared method to analyse the means (SD) of baseline variables, such as height or weight, from randomised controlled trials by Fujii et al., concluding that the probabilities that the reported distributions arose by chance were infinitesimally small. Subsequent testing of that chi-squared method, using simulation, suggested that the method was incorrect. This paper corrects the chi-squared method and tests its performance and the performance of Monte Carlo simulations and ANOVA to analyse the probability of random sampling. The corrected chi-squared method and ANOVA method became inaccurate when applied to means that were reported imprecisely. Monte Carlo simulations confirmed that baseline data from 158 randomised controlled trials by Fujii et al. were different to those from 329 trials published by other authors and that the distribution of Fujii et al.'s data were different to the expected distribution, both p < 10(-16) . The number of Fujii randomised controlled trials with unlikely distributions was less with Monte Carlo simulation than with the 2012 chi-squared method: 102 vs 117 trials with p < 0.05; 60 vs 86 for p < 0.01; 30 vs 56 for p < 0.001; and 12 vs 24 for p < 0.00001, respectively. The Monte Carlo analysis nevertheless confirmed the original conclusion that the distribution of the data presented by Fujii et al. was extremely unlikely to have arisen from observed data. The Monte Carlo analysis may be an appropriate screening tool to check for non-random (i.e. unreliable) data in randomised controlled trials submitted to journals.

Characterizing the molecular epidemiology of anaesthesia work area transmission of Staphylococcus aureus sequence type 5.

BACKGROUND: Staphylococcus aureus sequence type 5 (ST5) is an emerging global threat. AIM: To characterize the epidemiology of ST5 transmission in the anaesthesia work area. METHODS: The retrospective cohort study analysed transmitted, prophylactic antibiotic-resistant Staphylococcus aureus isolates involving anaesthesia work area reservoirs. Using whole-genome analysis, the epidemiology of ST5 transmission was characterized by reservoir(s) of origin, transmission location(s), portal of entry, and mode(s) of transmission. All patients were followed for at least 30 days for surgical site infection (SSI) development. FINDINGS: Forty-one percent (18/44; 95% confidence interval: 28-56%) of isolates were ST5. Provider hands were the reservoir of origin for 28% (5/18) of transmitted ST5 vs 4% (1/26) for other STs. Provider hands were the transmission location for 28% (5/18) of ST5 vs 7% (2/26) of other STs. Stopcock contamination occurred for 8% (1/13) of ST5 isolates vs 12% (3/25) of other STs. Sixty-three percent of transmission events occurring between cases on separate operative dates involved ST5. ST5 was more likely to harbour resistance traits (ST5 median (interquartile range) 3 (2-3) vs 2 (1-2) other STs; P < 0.001) and had greater resistance to cefazolin, piperacillin-tazobactam, and/or ciprofloxacin (ST5: 3 (2-3) vs 2 (1-3) other STs; P = 0.02). ST5 was associated with three of six SSIs. CONCLUSION: ST5 is prevalent among transmitted, prophylactic antibiotic-resistant isolates in the anaesthesia work area. Transmission involves provider hands and one patient to another on future date(s). ST5 is associated with a greater number of resistance traits and reduced in-vitro susceptibility vs other intraoperative meticillin-resistant S. aureus.

The relative efficacy of multiple syringe tip disinfection techniques against virulent staphylococcus contamination.

BACKGROUND: A recent study confirmed significant contamination of syringe tips following routine anaesthesia practice of at least 6 h in duration. AIM: We assessed the relative efficacy of clinically relevant syringe tip disinfection techniques following contamination with the hyper transmissible and more pathogenic Staphylococcus aureus sequence type 5 (S. aureus ST5) strain characteristic associated with increased strength of biofilm formation and greater desiccation tolerance. METHODS: Syringe tips (N=40) contaminated with S. aureus ST5 were randomized to 70% isopropyl pads with 10 or 60 s of drying time, scrubbing alcohol disinfection caps with 10 or 60 s of dwell time, or to non-scrubbing alcohol disinfection caps with 60 s of dwell time. The primary outcome was residual 24-h colony forming units (cfu) >10. RESULTS: Scrubbing disinfection caps were more effective than alcohol pads (25% (12/48) <10 cfu for scrubbing caps (10- or 60-s dwell times) vs 0% (0/48) <10 cfu for alcohol pads (10 or 60 s of drying time), Holm-Sidak adjusted P=0.0016). Scrubbing disinfection caps were more effective than non-scrubbing alcohol disinfection caps (25% (12/48) <10 cfu for scrubbing alcohol caps (10- or 60-s dwell times) vs 2% (1/48) for non-scrubbing alcohol caps (60-s dwell time), adjusted P=0.0087). CONCLUSIONS: Scrubbing alcohol caps are more effective than alcohol pads or non-scrubbing disinfecting caps for microbial reduction of syringe tips contaminated with the more pathogenic S. aureus ST5.

Transmission of Staphylococcus aureus in the anaesthesia work area has greater risk of association with development of surgical site infection when resistant to the prophylactic antibiotic administered for surgery.

BACKGROUND: The extent to which the transmission of prophylactic-antibiotic-resistant bacteria from the anaesthesia work area increases the risk of surgical site infection (SSI) is unknown. It was hypothesized that the risk of SSI would increase progressively from no transmission to transmission of prophylactic-antibiotic-resistant isolates. METHODS: This was a retrospective analysis of archival samples collected in two previously published studies with similar inclusion criteria and sample collection methodology (observational study 2009-2010 and randomized trial 2018-2019). Archival isolates were linked by barcode to all patient demographic and procedural information, including the prophylactic antibiotic administered, transmission and development of SSI. For this study, all archival isolates underwent prophylactic antibiotic susceptibility testing, and the ordered association of transmission of Staphylococcus aureus (no transmission, transmission of prophylactic-antibiotic-susceptible isolates and transmission of prophylactic-antibiotic-resistant isolates) with SSI was assessed. RESULTS: The risk of development of SSI was 2% (8/406) without S. aureus transmission, 11% (9/84) with transmission of S. aureus isolates that were susceptible to the prophylactic antibiotic used, and 18% (4/22) with transmission of prophylactic-antibiotic-resistant S. aureus isolates. The Cochrane-Armitage two-sided test for ordered association was P<0.0001. Treating these three groups as 0, 1 and 2, by exact logistic regression, the odds of SSI increased by 3.59 with each unit increase (95% confidence interval 1.92-6.64; P<0.0001). CONCLUSIONS: Transmission of S. aureus in the anaesthesia work area reliably increases the risk of SSI, especially when the isolates are resistant to the prophylactic antibiotic administered.

Desiccation tolerance is associated with Staphylococcus aureus hypertransmissibility, resistance and infection development in the operating room.

BACKGROUND: Desiccation tolerance increases Staphylococcus aureus survival and risk of transmission. A better understanding of factors driving intraoperative transmission of S. aureus pathogens may lead to innovative improvements in intraoperative infection control. AIMS: To determine whether desiccation tolerance is associated with intraoperative S. aureus transmission, and to examine typical transmission dynamics for desiccation-tolerant isolates in the operating room in order to provide the impetus for development of improved intraoperative infection control strategies. METHODS: S. aureus isolates (N=173) were collected from anaesthesia work area reservoirs in 274 operating room environments. Desiccation tolerance was assessed and the potential association with sequence type (ST) and clonal transmission was evaluated. Whole cell genome analysis and pulsed-field gel electrophoresis analysis were used to compare desiccation-tolerant isolates with causative organisms of infection. FINDINGS: S. aureus ST 5 isolates had greater desiccation tolerance than all other intraoperative STs [ST 5, N=34, median Day 2 colony-forming unit (cfu) survival 0.027% ± 0.029%; other STs, N=139, median Day 2 cfu survival 0.0091% ± 1.41%; corrected P=0.0001]. ST 5 was associated with increased risk of clonal transmission (relative risk 1.82, 95% confidence interval 1.23-2.71, P=0.003). ST 5 transmission was linked by whole cell genome analysis to postoperative infection. CONCLUSIONS: Increased desiccation tolerance is associated with intraoperative transmission of S. aureus ST 5 isolates that are linked to postoperative infection. Future work should determine whether attenuation of desiccation-tolerant, intraoperative ST 5 strains can impact the incidence of healthcare-associated infections.

Hospitals with briefer than average lengths of stays for common surgical procedures do not have greater odds of either re-admission or use of short-term care facilities.

We considered whether senior hospital managers and department chairs need to be concerned that small reductions in average hospital length of stay (LOS) may be associated with greater rates of re-admission, use of home health care, and/or transfers to short-term care facilities. The 2013 United States Nationwide Readmissions Database was used to study surgical Diagnosis Related Groups (DRG) with 1) national median LOS ≥3 days and 2) ≥10 hospitals in the database that each had ≥100 discharges for the DRG. Dependent variables were considered individually: 1) re-admission within 30 days of discharge, 2) discharge disposition to home health care, and/or 3) discharge disposition of transfer to short-term care facility (i.e., inpatient rehabilitation hospital or skilled nursing facility). While controlling for DRG, each one-day decrease in hospital median LOS was associated with an odds of re-admission nationwide of 0.95 (95% confidence interval [CI] 0.92-0.99; P=0.012), odds of disposition upon discharge being home care of 0.95 (95% CI 0.83-1.10; P=0.64), and odds of transfer to short-term care facility of 0.68 (95% CI 0.54-0.85; P=0.0008). Results were insensitive to the addition of patient-specific data. In the USA, patients at hospitals with briefer median LOS across multiple common surgical procedures did not have a greater risk for either hospital re-admission within 30 days of discharge or transfer to an inpatient rehabilitation hospital or a skilled nursing facility. The generalisable implication is that, across many surgical procedures, DRG-based financial incentives to shorten hospital stays seem not to influence post-acute care decisions.

[Allocating and scheduling operating room time]. / Zuweisung und Planung von Operationsraumkapazitäten Maximierung der Operationsraumeffizienz am Beispiel einer deutschen Universitätsklinik.

During the past decade many scientific advances have been made concerning the development of methodologies to maximize efficiency of surgical facilities through allocating and scheduling of operating rooms. In this article such a methodology is described. Using the analysis of historical data of surgical activity in a facility, future demand is predicted and planned. Part of the methodology includes principles and rules needed for the daily organization and operative management of surgical facilities. They are also derived from the same science and therefore the basis for rational and structured decision making. Medical aspects such as patient safety and free choice of day for surgery have higher priority than the economic goal of maximizing operating room efficiency.

Interactions between NMDA and AMPA glutamate receptor antagonists during halothane anesthesia in the rat.

There is increasing evidence that pharmacologic antagonism of glutamatergic neurotransmission can potentiate the anesthetic effects of drugs such as halothane. The purpose of this study was to examine the anesthetic interaction between glutamate receptor antagonists. A competitive NMDA receptor antagonist (CGS 19755) and an AMPA receptor antagonist (NBQX) were administered either alone or in combination prior to determination of the minimum alveolar concentration (MAC) for halothane in the rat. CGS 19755 caused a dose-dependent maximum reduction in halothane MAC of approximately 80%. Doses of NBQX, which were low enough to cause no change in MAC when administered alone, substantially reduced MAC when administered with subanesthetic doses of CGS 19755. This effect decreased as the dose of CGS 19755 was increased. Finally, halothane MAC was reduced to zero when NBQX, in a dose sufficient to reduce halothane MAC by approximately 35% if given alone, was added to a pharmacodynamically similar dose of CGS 19755. Although MAC is believed to predominantly reflect nocioception at the spinal cord level, the results suggests that pharmacologic blockade of glutamatergic neurotransmission is sufficient to result in deep levels of anesthesia. Further, the effect of combinations of NMDA and AMPA receptor antagonists on halothane MAC is consistent with an in vivo physiologic interaction between the NMDA and AMPA receptors.

Computer simulation of brain cooling during cardiopulmonary bypass.

A mathematical model of heat transport was used to analyze the effects of convection, metabolism, and conduction on the rate of brain cooling and the final brain temperature during cardiopulmonary bypass. Convection, a function of cerebral blood flow and arterial blood temperature, is by far the most important process to determine the rate of brain cooling. Arterial blood temperature almost entirely determines the final brain temperature. Although conduction (head surface cooling) has little effect on the rate of brain cooling or final brain temperature in adults, it may have moderate effects in infants. Brain metabolic heat production has insignificant direct effects on the rate of brain cooling and final brain temperature in both adults or infants. Computer simulation of convective cooling of the adult brain to 27 degrees C shows that, with routine perfusion techniques, brain temperature equilibration is rapid (16 minutes) and small brain-blood temperature gradients are achieved. Simulation of infant brain cooling to 17 degrees C shows that, to avoid excessive brain-blood temperature gradients, 22 to 26 minutes may be required to achieve brain temperature equilibration.

The brain uses mostly dissolved oxygen during profoundly hypothermic cardiopulmonary bypass.

BACKGROUND: During profoundly hypothermic cardiopulmonary bypass, cerebral venous oxygen saturation increases (eg, to 98% at 15 degrees C). We reanalyzed results of clinical studies to learn why. METHODS: One hundred sixty-eight cerebral oxygen transport measurements were available from 96 infants and children undergoing profoundly hypothermic cardiopulmonary bypass during repair of congenital heart defects. RESULTS: Dissolved oxygen accounted for 2% to 17% of arterial oxygen content, depending on the arterial oxygen partial pressure and hemoglobin concentration. The fraction of the cerebral metabolic rate for oxygen obtained from dissolved oxygen depended on pump flow, temperature, hemoglobin concentration, and arterial oxygen partial pressure (all p < 10(-3)). For "full-flow" cardiopulmonary bypass, temperatures less than 18 degrees C, and arterial oxygen partial pressure measurements more than 180 mm Hg, the mean +/- standard deviation of the fraction of cerebral metabolic rate for oxygen obtained from dissolved oxygen equaled 77% +/- 19%. CONCLUSIONS: Dissolved oxygen satisfies most of the brain's oxygen requirements during profound hypothermic cardiopulmonary bypass. This result reflects four properties of profound hypothermic cardiopulmonary bypass: (1) increases in hemoglobin's oxygen affinity due to profound hypothermia (which impairs oxygen transfer from hemoglobin to cerebral tissue), (2) use of hemodilution, (3) use of high arterial oxygen partial pressure, and (4) low cerebral metabolic rate of oxygen.

Post-ischemic RSR13 amplifies the effect of dizocilpine on outcome from transient focal cerebral ischemia in the rat.

In a recent study of focal cerebral ischemia in rats, pre-ischemic administration of the synthetic allosteric hemoglobin modifier RSR13 (2-[4-[[3,5-dimethylanilino) carbonyl] methyl] phenoxy]-2-methylproprionic acid) reduced cerebral infarct size when combined with the NMDA receptor antagonist dizocilpine (MK-801) but not when given alone. We hypothesized that post-ischemic RSR13 administration would enhance neuroprotection afforded by NMDA receptor antagonism in a rat model of transient middle cerebral artery occlusion (MCAO). Fasted normothermic Wistar rats underwent 75 min of temporary MCAO. At onset of reperfusion, rats randomly received: (1) 0.9% NaCl (vehicle) i.v. alone (n=16); (2) 0.9% NaCl+dizocilpine (0.25 mg/kg) i.v. (n=16); or (3) RSR13 (150 mg/kg)+dizocilpine (0.25 mg/kg) i.v. (n=17). Seven days later, neurologic deficit and cerebral infarct size were determined. Dizocilpine alone compared to vehicle reduced mean+/-S.D. subcortical (52+/-24 mm(3) vs. 122+/-64 mm(3), P=0.003) and cortical (35+/-35 mm(3) vs. 125+/-72 mm(3), P=0.00074) infarct volumes. When compared to dizocilpine alone, the combination of RSR13+dizocilpine further reduced subcortical (37+/-14 mm(3) vs. 52+/-24 mm(3), P=0. 034) and cortical (8+/-19 mm(3) vs. 35+/-35 mm(3), P=0.018) infarct size. RSR13+dizocilpine improved neurologic scores vs. either dizocilpine alone (P=0.0014) or vehicle (P=10(-7)). The combination of NMDA receptor antagonism and a RSR13 mediated rightward shift of the oxy-hemoglobin dissociation curve improved outcome from MCAO. Because this occurred after reperfusion, our results suggest that the post-ischemic brain continues to suffer from hypoperfusion defects, which are amenable to therapy by enhanced O(2) delivery. The results also support the concept that neuroprotective strategies, which combine drugs with different mechanisms of action, may yield cumulative benefits.

Chronic hypoxemia causes extracellular glutamate concentration to increase in the cerebral cortex of the near-term fetal sheep.

Fetal hypoxia is an important cause of neurologic morbidity and mortality. Hypoxia-induced increase in extracellular glutamate concentration can lead to excitotoxic neuronal death in adults. The objective of this study was to test whether chronic fetal hypoxemia increases extracellular glutamate concentration in the unanesthetized intact cerebral cortex of the near-term fetal sheep. Microdialysis probes were implanted into the parasagittal parietal cortex and periventricular white matter of near-term fetal sheep. At 124 +/- 1 days of gestation, extracellular glutamate concentration was determined before and during 24 h of fetal hypoxemia. Chronic hypoxemia was produced by tightening a vascular occluder placed around the maternal common iliac artery. Larger decreases in fetal arterial oxygen content were associated with larger increases in extracellular glutamate concentration in the parietal cortex (Kendall's tau = 0.81, N = 7, p = 0.005). No such relationship was detected in the periventricular white matter. Chronic hypoxemia increases extracellular glutamate concentration in the intact cerebral cortex of the unanesthetized near-term fetal sheep.

Biomechanical evaluation of Caspar and Cervical Spine Locking Plate systems in a cadaveric model.

There exist two markedly different instrumentation systems for the anterior cervical spine: the Cervical Spine Locking Plate (CSLP) system, which uses unicortical screws with a locking hub mechanism for attachment, and the Caspar Trapezial Plate System, which is secured with unlocked bicortical screws. The biomechanical stability of these two systems was evaluated in a cadaveric model of complete C5-6 instability. The immediate stability was determined in six loading modalities: flexion, extension, right and left lateral bending, and right and left axial rotation. Biomechanical stability was reassessed following fatigue with 5000 cycles of flexion-extension, and finally, the spines were loaded in flexion until the instrumentation failed. The Caspar system stabilized significantly in flexion before (p < 0.05) but not after fatigue, and it stabilized significantly in extension before (p < 0.01) and after fatigue (p < 0.01). The CSLP system stabilized significantly in flexion before (p < 0.01) but not after fatigue, and it did not stabilize in extension before or after fatigue. The moment needed to produce failure in flexion did not differ substantially between the two plating systems. The discrepancy in the biomechanical stability of these two systems may be due to differences in bone screw fixation.

Bolus maternal cocaine administration does not produce a large increase in fetal sheep cerebral cortical glutamate concentration.

Human cocaine use during pregnancy may result in postnatal neurologic dysfunction and abnormal behavior. L-Glutamate, the major excitatory neurotransmitter in the brain, plays an important role in cerebral cortical development. An optimal level of glutamate is required for normal neuronal development. We tested whether acute cocaine exposure produces large increases in glutamate release in the intact cerebral cortex of the near-term fetal sheep. Cocaine 3.0 mg kg(-1) IV bolus produced the expected increase in maternal and fetal mean arterial pressure, increase in fetal heart rate, decrease in uterine blood flow, and decrease in fetal arterial blood pO2 (N = 5). The percentage increases in extracellular glutamate concentration in the fetal cerebral cortex measured by in utero microdialysis were 7%, 15%, 17%, 17%, and 43% in each fetus (upper 95% confidence bound for the median = 43%). We conclude that if cocaine increases glutamate concentration in the developing cerebral cortex, the increase in magnitude is small relative to the changes produced by other interventions such as ethanol or umbilical cord occlusion. Mechanisms other than increases in cerebral cortical glutamate concentration probably contribute to the neurologic injury associated with prenatal cocaine exposure.

Research synthesis of controlled studies evaluating the effect of hypocapnia and airway protection on cerebral outcome.

Hyperventilation is a standard method of treating patients with intracranial hypertension. I reviewed all the relevant peer-reviewed literature to identify the documented benefits of hyperventilation as treatment for cerebral disease. Studies were identified by searches of the Medline database between 1966 and September 1996, interviews with experts, and reviews of reference lists. Retained manuscripts reported results of a human or animal controlled trial that tested effect of hyperventilation and/or systemic hypocapnia on mortality, histopathology, or neurologic examination. Studies could be either randomized or observational and need not have been blinded. I found that for no clinical studies of cerebral disease, other than in acute head injury patients, was there any suggestion of a clinical benefit from hyperventilation. Three controlled, observational studies examined effects of airway management and ventilatory support in head-injured patients. These studies found that maintaining such patients hypocapnic, versus spontaneously breathing without ventilatory support, decreased mortality. However, by design the studies could not establish whether hypocapnia itself contributed to the decreased mortality. Two clinical studies examined the effect of PaCO2 itself in patients with head injury. In both, hypocapnic patients did not have better neurologic outcome. In conclusion, securing the airway and supporting ventilation probably reduces mortality in unconscious, neurosurgical patients. However, there are virtually no clinical data that hypocapnia improves outcome in patients with cerebral disease.