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1.  Steroids In caRdiac Surgery (SIRS) trial: acute kidney injury substudy protocol of an international randomised controlled trial 
BMJ Open  2014;4(3):e004842.
Introduction
Steroids In caRdiac Surgery trial (SIRS) is a large international randomised controlled trial of methylprednisolone or placebo in patients undergoing cardiac surgery with the use of a cardiopulmonary bypass pump. At the time of surgery, compared with placebo, methylprednisolone divided into two intravenous doses of 250 mg each may reduce the risk of postoperative acute kidney injury (AKI).
Methods and analysis
With respect to the study schedule, over 7000 substudy eligible patients from 81 centres in 18 countries were randomised in December 2013. The authors will use a logistic regression to estimate the adjusted OR of methylprednisolone versus placebo on the primary outcome of AKI in the 14 days following surgery (a postoperative increase in serum creatinine of ≥50%, or ≥26.5 μmol/L, from the preoperative value). The stage of AKI will also be considered, as will the outcome of AKI in those with and without preoperative chronic kidney disease. After receipt of grant funding, the authors began to record additional perioperative serum creatinine measurements in consecutive patients enrolled at substudy participating centres, and patients were invited to enroll in a 6-month serum creatinine collection. In these trial subpopulations, the authors will consider the outcome of AKI defined in alternate ways, and the outcome of a 6-month change in kidney function from the preoperative value.
Ethics and dissemination
The authors were competitively awarded a grant from the Canadian Institutes of Health Research for this SIRS AKI substudy. Ethics approval was obtained for additional serum creatinine recordings in consecutive patients enrolled at participating centres. The additional kidney data collection first began for patients enrolled after 1 March 2012. In patients who provided consent, the last 6-month kidney outcome data will be collected in 2014. The results will be reported no later than 2015.
Clinical Trial Registration
Number NCT00427388.
doi:10.1136/bmjopen-2014-004842
PMCID: PMC3948633  PMID: 24598306
2.  Aspirin and clonidine in non-cardiac surgery: acute kidney injury substudy protocol of the Perioperative Ischaemic Evaluation (POISE) 2 randomised controlled trial 
BMJ Open  2014;4(2):e004886.
Introduction
Perioperative Ischaemic Evaluation-2 (POISE-2) is an international 2×2 factorial randomised controlled trial of low-dose aspirin versus placebo and low-dose clonidine versus placebo in patients who undergo non-cardiac surgery. Perioperative aspirin (and possibly clonidine) may reduce the risk of postoperative acute kidney injury (AKI).
Methods and analysis
After receipt of grant funding, serial postoperative serum creatinine measurements began to be recorded in consecutive patients enrolled at substudy participating centres. With respect to the study schedule, the last of over 6500 substudy patients from 82 centres in 21 countries were randomised in December 2013. The authors will use logistic regression to estimate the adjusted OR of AKI following surgery (compared with the preoperative serum creatinine value, a postoperative increase ≥26.5 μmol/L in the 2 days following surgery or an increase of ≥50% in the 7 days following surgery) comparing each intervention to placebo, and will report the adjusted relative risk reduction. Alternate definitions of AKI will also be considered, as will the outcome of AKI in subgroups defined by the presence of preoperative chronic kidney disease and preoperative chronic aspirin use. At the time of randomisation, a subpopulation agreed to a single measurement of serum creatinine between 3 and 12 months after surgery, and the authors will examine intervention effects on this outcome.
Ethics and dissemination
The authors were competitively awarded a grant from the Canadian Institutes of Health Research for this POISE-2 AKI substudy. Ethics approval was obtained for additional kidney data collection in consecutive patients enrolled at participating centres, which first began for patients enrolled after January 2011. In patients who provided consent, the remaining longer term serum creatinine data will be collected throughout 2014. The results of this study will be reported no later than 2015.
Clinical Trial Registration Number
NCT01082874.
doi:10.1136/bmjopen-2014-004886
PMCID: PMC3939660  PMID: 24568963
Surgery; Epidemiology
3.  Choice of anesthetic technique on plasma concentrations of interleukins and cell adhesion molecules 
Background
Whether inflammatory responses to surgery are comparably activated during total intravenous anesthesia (TIVA) and during volatile anesthesia remains unclear. We thus compared the perioperative effects of TIVA and isoflurane anesthesia on plasma concentrations of proinflammatory and anti-inflammatory interleukins and cell adhesion molecules.
Methods
Patients having laparoscopic cholecystectomies were randomly allocated to two groups: 44 were assigned to TIVA and 44 to isoflurane anesthesia. IL-1β, IL-6, IL-8, IL-10, IL-13, and the cellular adhesion molecules intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were determined preoperatively, before incision, and at 2 and 24 hours postoperatively. Our primary outcomes were area-under-the-curve cytokine and adhesion molecule concentrations over 24 postoperative hours.
Results
The only statistically significant difference in area-under-the-curve concentrations was for IL-6, which was greater in patients given isoflurane:78 (95% confidence interval (CI): 52 to 109) pg/ml versus 33 (22 to 50) pg/ml, P= 0.006. Two hours after surgery, IL-6 was significantly greater than baseline in patients assigned to isoflurane: 47 (95% CI: 4 to 216, P<0.001) pg/ml versus 18 (95%CI: 4 to 374, P<0.001) pg/ml in the TIVA group. In contrast, IL-10 was significantly greater in patients assigned to TIVA: 20 (95% CI: 2 to 140, P<0.001) pg/ml versus 12 (95% CI: 3 to 126, P<0.001) pg/ml. By 24 hours after surgery, concentrations were generally similar between study groups and similar to baseline values.
Conclusion
The only biomarker whose postoperative area-under-the-curve concentrations differed significantly as a function of anesthetic management was IL-6. Two hours after surgery, IL-6 concentrations were significantly greater in patients given isoflurane than TIVA. However, the differences were modest and seem unlikely to prove clinically important. Further studies are needed.
doi:10.1186/2047-0525-2-8
PMCID: PMC3964335  PMID: 24472144
Inhalation anesthetics; Intravenous anesthetics; Propofol; Cell adhesion molecules; Interleukins
5.  Continuous Femoral Nerve Blocks: Decreasing Local Anesthetic Concentration to Minimize Quadriceps Femoris Weakness 
Anesthesiology  2012;116(3):665-672.
Background
Whether decreasing the local anesthetic concentration during a continuous femoral nerve block results in less quadriceps weakness remains unknown.
Methods
Preoperatively, bilateral femoral perineural catheters were inserted in patients undergoing bilateral knee arthroplasty (n = 36) at a single clinical center. Postoperatively, right-sided catheters were randomly assigned to receive perineural ropivacaine of either 0.1% (basal 12 mL/h; bolus 4 mL) or 0.4% (basal 3 mL/h; bolus 1 mL), with the left catheter receiving the alternative concentration/rate in an observer- and subject-masked fashion. The primary endpoint was the maximum voluntary isometric contraction of the quadriceps femoris muscles the morning of postoperative day 2. Equivalence of treatments would be concluded if the 95% confidence interval for the difference fell within the interval of −20% to 20%. Secondary endpoints included active knee extension, passive knee flexion, tolerance to cutaneous electrical current applied over the distal quadriceps tendon, dynamic pain scores, opioid requirements, and ropivacaine consumption.
Results
Quadriceps maximum voluntary isometric contraction for limbs receiving 0.1% ropivacaine was a mean (SD) of 13 (8) N·m, versus 12 (8) N·m for limbs receiving 0.4% [intra-subject difference of 3 (40) percentage points; 95% CI −10 to 17; p = 0.63]. Because the 95% confidence interval fell within prespecified tolerances, we conclude that the effect of the two concentrations were equivalent. Similarly, there were no statistically significant differences in secondary endpoints.
Conclusions
For continuous femoral nerve blocks, we found no evidence that local anesthetic concentration and volume influence block characteristics, suggesting that local anesthetic dose (mass) is the primary determinant of perineural infusion effects.
doi:10.1097/ALN.0b013e3182475c35
PMCID: PMC3288409  PMID: 22293719
6.  Temperature Monitoring and Perioperative Thermoregulation 
Anesthesiology  2008;109(2):318-338.
Most clinically available thermometers accurately report the temperature of whatever tissue is being measured. The difficulty is that no reliably core-temperature measuring sites are completely non-invasive and easy to use — especially in patients not having general anesthesia. Nonetheless, temperature can be reliably measured in most patients. Body temperature should be measured in patients having general anesthesia exceeding 30 minutes in duration, and in patients having major operations under neuraxial anesthesia.
Core body temperature is normally tightly regulated. All general anesthetics produce a profound dose-dependent reduction in the core temperature triggering cold defenses including arterio-venous shunt vasoconstriction and shivering. Anesthetic-induced impairment of normal thermoregulatory control, and the resulting core-to-peripheral redistribution of body heat, is the primary cause of hypothermia in most patients. Neuraxial anesthesia also impairs thermoregulatory control, although to a lesser extant than general anesthesia. Prolonged epidural analgesia is associated with hyperthermia whose cause remains unknown.
doi:10.1097/ALN.0b013e31817f6d76
PMCID: PMC2614355  PMID: 18648241
9.  Perioperative Acupuncture and Related Techniques 
Anesthesiology  2005;102(5):1031-1078.
Acupuncture and related techniques are increasingly practiced in conventional medical settings, and the number of patients willing to use these techniques is increasing. Despite more than 30 years of research, the exact mechanism of action and efficacy of acupuncture have not been established. Furthermore, most aspects of acupuncture have yet to be adequately tested. There thus remains considerable controversy about the role of acupuncture in clinical medicine.
Acupuncture apparently does not reduce volatile anesthetic requirement by a clinically important amount. However, preoperative sedation seems to be a promising application of acupuncture in perioperative settings. Acupuncture may be effective for postoperative pain relief but requires a high level of expertise by the acupuncture practitioner. Acupuncture and related techniques can be used for treatment and prophylaxis of postoperative nausea and vomiting in routine clinical practice in combination with, or as an alternative to, conventional antiemetics when administered before induction of general anesthesia.
Summary Statement: The use of acupuncture for perioperative analgesia, nausea and vomiting, sedation, anesthesia, and complications is reviewed.
PMCID: PMC1475803  PMID: 15851892
10.  Cutaneous Heat Loss with Three Surgical Drapes, One Impervious to Moisture 
Anesthesia and analgesia  2005;100(3):738-contents.
A new surgical drape, which is impervious to moisture, presumably reduces evaporative heat loss. We compared cutaneous heat loss and skin temperature in volunteers covered with this drape to two conventional surgical drapes (Large Surgical Drape and Medline Proxima). With IRB approval and informed consent, we calculated cutaneous heat loss and skin-surface temperatures from 15 area-weighted thermal flux transducers in 8 volunteers. In random order, each of the drapes was evaluated with dry transducers and moistened transducers (simulating wet skin). After a 20-minute uncovered control period, volunteers were covered from the neck down for 40 minutes. Data were recorded continuously and averaged over 10-minutes. Results were similar for all three drapes for dry or moist conditions. Under dry conditions, baseline heat loss was 82±14 watts (W) and decreased 30% with a surgical drape (P<0.001). Under moist conditions, baseline heat loss was 231±45 W and decreased 29% with a drape covering (P<0.001). Moist skin increased heat loss 282% (P<0.001). There were no clinically important differences in skin temperature among the covers with dry or moist skin. Moist skin increased heat loss nearly three-fold, but there were no differences among the drapes. We conclude that loss is comparable with impervious and conventional drapes with either moist or dry skin.
doi:10.1213/01.ANE.0000143954.98285.63
PMCID: PMC1351377  PMID: 15728062
Evaporation; Heat flux; Insulation; Surgical drapes; Sweat; Temperature; Thermoregulation
11.  Correlation between Bispectral Index, Observational Sedation Scale, and Lower Esophageal Sphincter Pressure in volunteers using dexmedetomidine or propofol 
Summary
Background
Many anesthetics reduce lower esophageal sphincter pressure (LESP) and consequently the gastro-esophageal pressure gradient (GEPG); thus they may promote gastro-esophageal reflux and contribute to aspiration pneumonia. Our goals were to evaluate the association between LESP and 2 measures of sedation: bispectral index (BIS) and the responsiveness component of the Observer’s Assessment of Alertness score (OAA/S).
Material/Methods
Eleven healthy volunteers were each sedated on 2 separate days. Subjects were given sedative infusions of increasing target plasma concentrations of dexmedetomidine or propofol. LESP and GEPG were recorded after starting each infusion phase. Generalized estimating equation modeling was used to assess the relationship between LESP and, respectively, BIS and OAA/S. The existence of a drug-dependent association was evaluated within these models by testing an interaction term. Wald tests were used to evaluate the relationships within the models.
Results
We found a significant relationship between LESP and BIS (P=0.0043) after adjusting for the main effect of sedative type – a deepening of sedation as measured by a decrease in BIS of 10% was associated with a decrease [Bonferroni-adjusted 95% CI] in LESP of −1.34 [−2.39, −0.29] mmHg. After adjusting for the main effect of sedative drug, LESP significantly declined with declining OAA/S (P=0.001); a unit decrease of OAA/S was associated with a decrease [Bonferroni-adjusted 95% CI] in LESP of −2.01 [−3.20, −0.81] mmHg.
Conclusions
Deeper sedation, as measured by either BIS or OAA/S, significantly reduces LESP.
doi:10.12659/MSM.883484
PMCID: PMC3560568  PMID: 23018351
BIS; lower esophageal sphincter; dexmedetomidine; propofol
12.  Women Have the Same Desflurane MAC as Men: A Prospective Study 
Anesthesiology  2003;99(5):1062-1065.
Background:
Women generally report greater sensitivity to pain than do men, and healthy young women require 20% more anesthetic than healthy age-matched men to prevent movement in response to noxious electrical stimulation. In contrast, MAC for xenon is 26% less in elderly Japanese women than in elderly Japanese men. Whether anesthetic requirement is similar in men and women thus remains in dispute. We therefore tested the hypothesis that the desflurane concentration required to prevent movement in response to skin incision (MAC) differs in men and women.
Methods:
Using the Dixon “up and down” method, we determined MAC for desflurane in 15 female and 15 male patients undergoing surgery (18–40 yr).
Results:
MAC was 6.2 ± 0.4% desflurane for women vs. 6.0 ± 0.3% for men (P = 0.31), a difference of only 3%. These data provide 90% power to detect a 9% difference between the groups.
Conclusion:
MAC of desflurane did not differ between young men and women undergoing surgery with a true surgical incision. While pain sensitivity may differ in women versus men, MAC of desflurane does not.
Summary Statement:
MAC for desflurane was similar in young adult women and men (6.2 ± 0.4% desflurane for women vs. 6.0 ± 0.3% for men; P = 0.31). This contrasts with previous results in which anesthetic requirement was based on the response to electrical stimulation and with studies showing that women report more pain than men.
PMCID: PMC1552095  PMID: 14576540
13.  Blood Storage Duration and Biochemical Recurrence of Cancer After Radical Prostatectomy 
Mayo Clinic Proceedings  2011;86(2):120-127.
OBJECTIVE: To test the hypothesis that perioperative transfusion of allogeneic and autologous red blood cells (RBCs) stored for a prolonged period speeds biochemical recurrence of prostate cancer after prostatectomy.
PATIENTS AND METHODS: We evaluated biochemical prostate cancer recurrence in men who had undergone radical prostatectomy and perioperative blood transfusions from July 6, 1998, through December 27, 2007. Those who received allogeneic blood transfusions were assigned to nonoverlapping “younger,” “middle,” and “older” RBC storage duration groups. Those who received autologous RBC transfusions were analyzed using the maximum storage duration as the primary exposure. We evaluated the association between RBC storage duration and biochemical recurrence using multivariable Cox proportional hazards regression.
RESULTS: A total of 405 patients received allogeneic transfusions. At 5 years, the biochemical recurrence–free survival rate was 74%, 71%, and 76% for patients who received younger, middle, and older RBCs, respectively; our Cox model indicated no significant differences in biochemical recurrence rates between the groups (P=.82; Wald test). Among patients who received autologous transfusions (n=350), maximum RBC age was not significantly associated with biochemical cancer recurrence (P=.95). At 5 years, the biochemical recurrence–free survival rate was 85% and 81% for patients who received younger and older than 21-day-old RBCs, respectively.
CONCLUSION: In patients undergoing radical prostatectomy who require RBC transfusion, recurrence risk does not appear to be independently associated with blood storage duration.
The authors evaluated the association between duration of red blood cell storage and biochemical recurrence of cancer in men who had undergone radical prostatectomy and perioperative blood transfusions. Recurrence risk does not appear to be independently associated with blood storage duration.
doi:10.4065/mcp.2010.0313
PMCID: PMC3031436  PMID: 21282486
14.  Use of α2-Agonists in Neuroanesthesia: An Overview 
The Ochsner Journal  2011;11(1):57-69.
α2-Agonists are a novel class of drugs with mechanisms of action that differ from other commonly used anesthetic drugs. They have neuroprotective, cardioprotective, and sedative effects. These unique characteristics make them potentially useful during neuroanesthesia and intensive care. We review the effects of dexmedetomidine on cerebral blood flow and cerebral metabolism, along with recent advances in using α2-agonists in neuroanesthesia and neurointensive care.
PMCID: PMC3096156  PMID: 21603337
Alpha-2 agonist; anesthesia; dexmedetomidine; neuroanesthesia; neuroprotection
15.  Endobronchial intubation detected by insertion depth of endotracheal tube, bilateral auscultation, or observation of chest movements: randomised trial 
Objective To determine which bedside method of detecting inadvertent endobronchial intubation in adults has the highest sensitivity and specificity.
Design Prospective randomised blinded study.
Setting Department of anaesthesia in tertiary academic hospital.
Participants 160 consecutive patients (American Society of Anesthesiologists category I or II) aged 19-75 scheduled for elective gynaecological or urological surgery.
Interventions Patients were randomly assigned to eight study groups. In four groups, an endotracheal tube was fibreoptically positioned 2.5-4.0 cm above the carina, whereas in the other four groups the tube was positioned in the right mainstem bronchus. The four groups differed in the bedside test used to verify the position of the endotracheal tube. To determine whether the tube was properly positioned in the trachea, in each patient first year residents and experienced anaesthetists were randomly assigned to independently perform bilateral auscultation of the chest (auscultation); observation and palpation of symmetrical chest movements (observation); estimation of the position of the tube by the insertion depth (tube depth); or a combination of all three (all three).
Main outcome measures Correct and incorrect judgments of endotracheal tube position.
Results 160 patients underwent 320 observations by experienced and inexperienced anaesthetists. First year residents missed endobronchial intubation by auscultation in 55% of cases and performed significantly worse than experienced anaesthetists with this bedside test (odds ratio 10.0, 95% confidence interval 1.4 to 434). With a sensitivity of 88% (95% confidence interval 75% to 100%) and 100%, respectively, tube depth and the three tests combined were significantly more sensitive for detecting endobronchial intubation than auscultation (65%, 49% to 81%) or observation(43%, 25% to 60%) (P<0.001). The four tested methods had the same specificity for ruling out endobronchial intubation (that is, confirming correct tracheal intubation). The average correct tube insertion depth was 21 cm in women and 23 cm in men. By inserting the tube to these distances, however, the distal tip of the tube was less than 2.5 cm away from the carina (the recommended safety distance, to prevent inadvertent endobronchial intubation with changes in the position of the head in intubated patients) in 20% (24/118) of women and 18% (7/42) of men. Therefore optimal tube insertion depth was considered to be 20 cm in women and 22 cm in men.
Conclusion Less experienced clinicians should rely more on tube insertion depth than on auscultation to detect inadvertent endobronchial intubation. But even experienced physicians will benefit from inserting tubes to 20-21 cm in women and 22-23 cm in men, especially when high ambient noise precludes accurate auscultation (such as in emergency situations or helicopter transport). The highest sensitivity and specificity for ruling out endobronchial intubation, however, is achieved by combining tube depth, auscultation of the lungs, and observation of symmetrical chest movements.
Trial registration NCT01232166.
doi:10.1136/bmj.c5943
PMCID: PMC2977961  PMID: 21062875
16.  Oral Microbial and Respiratory Status of Persons with Mental Retardation/Intellectual & Developmental Disability – An Observational Cohort Study 
Objective
The objective of this study was to determine the prevalence of select microorganisms in oral biofilms and to investigate relationships between oral and respiratory status in persons with mental retardation/intellectual and developmental disabilities (IDD).
Study Design
We conducted a 6-month-long observational cohort study with 63 persons with IDD. Oral examinations, oral sampling, and medical record reviews were performed at baseline and then monthly. Polymerase chain reaction (PCR) was used to analyze all baseline oral samples for the presence of Streptococcus pneumoniae (S. pneumoniae), Methicillin-Resistant Staphylococcus aureus (MRSA), Prevotella melaninogenica (P. melaninogenica) and Candida albicans (C. albicans). PCR analyses were also performed on participants’ samples collected in the month prior to being diagnosed with a respiratory infection.
Results
All subjects had P. melaninogenica detected by PCR in their oral samples. Fifty-five percent (35 of 63) of participants had S. pneumoniae, MRSA and C. albicans in their oral samples at baseline. No dental decay was detected clinically, oral hygiene was fair, and dysphagia was common. During the 6 months of the study, there were 22 respiratory infections (35% of participants) – 12 pneumonias, 7 sinusitis, 1 bronchitis, and 1 upper respiratory tract infection. Participants with microorganisms in their baseline samples were significantly more likely to develop any respiratory infection and those who had poor oral status were significantly more likely to develop pneumonia. Almost 60% of participants who developed respiratory infections had the same microorganism detected in the sample collected in the month prior to infection as had been detected in their baseline sample.
Conclusion
Potentially pathogenic microorganisms in the oral cavity and poor oral status significantly increased the risk of developing respiratory infections, including pneumonia, in persons with IDD. The results suggest that colonization with these microorganisms may persist despite routine tooth brushing. Meticulous comprehensive oral hygiene of the oral cavity may be needed to reduce oropharyngeal microbial load.
doi:10.1016/j.tripleo.2009.06.027
PMCID: PMC2763931  PMID: 19748295
17.  Health-Related Quality-of-Life After Hip Arthroplasty With and Without an Extended-Duration Continuous Posterior Lumbar Plexus Nerve Block: A Prospective, One-Year Follow-Up of a Randomized, Triple-Masked, Placebo-Controlled Study 
Anesthesia and analgesia  2009;109(2):586-591.
Background
We previously reported that extending an overnight continuous posterior lumbar plexus nerve block to 4 days after hip arthroplasty provides clear benefits during the perineural infusion in the immediate postoperative period. However, it remains unknown if the extended infusion improves subsequent health-related quality-of-life.
Methods
Patients undergoing hip arthroplasty received a posterior lumbar plexus perineural infusion of ropivacaine 0.2% from surgery until the following morning, at which time patients were randomized to either continue perineural ropivacaine (n=24) or normal saline (n=23) in a double-masked fashion. Patients were discharged with their catheter and a portable infusion pump, and catheters were removed on postoperative day 4. Health-related quality-of-life was measured using the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index preoperatively and then at 7 days, as well as 1, 2, 3, 6, and 12 months after surgery. The WOMAC evaluates 3 dimensions of health-related quality-of-life: pain, stiffness, and physical functional disability (global score of 0–96, lower scores indicate lower levels of symptoms or physical disability). For inclusion in the primary analysis, we required a minimum of 3 of the 6 time points, including day 7 and at least 2 of months 3, 6, and 12.
Results
The 2 treatment groups had similar global WOMAC scores for the mean area under the curve calculations (point estimate for the difference in mean area under the curve for the 2 groups [extended infusion group – overnight infusion group] = 0.8, 95% confidence interval: −5.3 to +6.8 [−5.5% to +7.1%]; p=0.80) and at all individual time points (p>0.05).
Conclusions
This investigation found no evidence that extending an overnight continuous posterior lumbar plexus nerve block to 4 days improves (or worsens) subsequent health-related quality-of-life between 7 days and 12 months after hip arthroplasty.
doi:10.1213/ane.0b013e3181a9db5d
PMCID: PMC2725431  PMID: 19608835
18.  The Effects of Local Anesthetic Concentration and Dose on Continuous Infraclavicular Nerve Blocks: A Multicenter, Randomized, Observer-Masked, Controlled Study 
Anesthesia and analgesia  2009;108(1):345-350.
BACKGROUND
It remains unclear whether local anesthetic concentration or total drug dose is the primary determinant of continuous peripheral nerve block effects. The only previous investigation, involving continuous popliteal-sciatic nerve blocks, specifically addressing this issue reported that insensate limbs were far more common with higher volumes of relatively dilute ropivacaine compared with lower volumes of relatively concentrated ropivacaine. However, it remains unknown if this relationship is specific to the sciatic nerve in the popliteal fossa or whether it varies depending on anatomic location. We therefore tested the null hypothesis that providing ropivacaine at different concentrations and rates, but at an equal total basal dose, produces comparable effects when used in a continuous infraclavicular brachial plexus block.
METHODS
Preoperatively, an infraclavicular catheter was inserted using the coracoid approach in patients undergoing moderately painful orthopedic surgery distal to the elbow. Patients were randomly assigned to receive a postoperative perineural ropivacaine infusion of either 0.2% (basal 8 mL/h, bolus 4 mL) or 0.4% (basal 4 mL/h, bolus 2 mL) through the second postoperative day. Both groups, therefore, received 16 mg of ropivacaine each hour with a possible addition of 8 mg every 30 min via a patient-controlled bolus dose. Our primary end point was the incidence of an insensate limb during the 24-h period beginning the morning after surgery. Secondary end points included analgesia and patient satisfaction.
RESULTS
Patients given 0.4% ropivacaine (n = 27) experienced an insensate limb, a mean (sd) of 1.8 (1.6) times, compared with 0.6 (0.9) times for subjects receiving 0.2% ropivacaine (n = 23; estimated difference = 1.2 episodes, 95% confidence interval, 0.5–1.9 episodes; P = 0.001). Satisfaction with postoperative analgesia (scale 0–10, 10 = highest) was scored a median (25th–75th percentiles) of 10.0 (8.0–10.0) in Group 0.2% and 7.0 (5.3–8.9) in Group 0.4% (P = 0.018). Analgesia was similar in each group.
CONCLUSIONS
For continuous infraclavicular nerve blocks, local anesthetic concentration and volume influence perineural infusion effects in addition to the total mass of local anesthetic administered. Insensate limbs were far more common with smaller volumes of relatively concentrated ropivacaine. This is the opposite of the relationship previously reported for continuous popliteal-sciatic nerve blocks. The interaction between local anesthetic concentration and volume is thus complex and varies among catheter locations.
doi:10.1213/ane.0b013e31818c7da5
PMCID: PMC2745828  PMID: 19095871
19.  Effects of Local Anesthetic Concentration and Dose on Continuous Interscalene Nerve Blocks: A Dual-Center, Randomized, Observer-Masked, Controlled Study 
Background and Objectives:
It is currently unknown if the primary determinant of continuous peripheral nerve block effects is simply total drug dose, or whether local anesthetic concentration and/or volume have an influence. We therefore tested the null hypothesis that providing ropivacaine at different concentrations and rates—but at an equal total basal dose—produces similar effects when used in a continuous interscalene nerve block.
Methods:
Preoperatively, an interscalene perineural catheter was inserted using the anteriolateral approach in patients undergoing moderately painful shoulder surgery. Subjects were randomly assigned to receive a postoperative perineural infusion of either 0.2% ropivacaine (basal 8 mL/h, bolus 4 mL) or 0.4% ropivacaine (basal 4 mL/h, bolus 2 mL) through the second postoperative day. Our primary end point was the incidence of an insensate hand/finger during the 24-hours beginning the morning following surgery.
Results:
The incidence of an insensate hand/finger did not differ between the treatment groups (n=50) to a statistically significant degree (0.2% ropivacaine mean [SD] of 0.8 [1.3] times; 0.4% ropivacaine mean 0.3 [0.6] times; estimated difference=0.5 episodes, 95% confidence interval, −0.1 to 1.1 episodes; p=0.080). However, this is statistically inconclusive given the confidence interval. In contrast, pain (p=0.020) and dissatisfaction (p=0.011) were greater in patients given 0.4% ropivacaine.
Conclusions:
For continuous interscalene nerve blocks, the 95% confidence interval (plausible differences in the incidence of an insensate hand/finger) contains values ranging from a clinically important disadvantage (1.1) to a clinically unimportant advantage (−0.1) for the lower concentration. Given the statistically inconclusive results and design limitations of the current study, further research on this issue is warranted. In contrast, providing a lower concentration of local anesthetic at a higher basal rate provided superior analgesia. These relationships are different than previously reported for continuous popliteal-sciatic nerve blocks. The interaction between local anesthetic concentration and volume is thus complex and varies among catheter locations.
PMCID: PMC2711692  PMID: 19258966
anesthesia; continuous peripheral nerve block; continuous interscalene nerve block; patient-controlled regional analgesia; perineural local anesthetic infusion
20.  Ambulatory Continuous Posterior Lumbar Plexus Nerve Blocks after Hip Arthroplasty 
Anesthesiology  2008;109(3):491-501.
Background
The authors tested the hypotheses that after hip arthroplasty, ambulation distance is increased and the time required to reach three specific readiness-for-discharge criteria is shorter with a 4-day ambulatory continuous lumbar plexus block (cLPB) than with an overnight cLPB.
Methods
A cLPB consisting of 0.2% ropivacaine was provided from surgery until the following morning. Patients were then randomly assigned either to continue ropivacaine or to be switched to normal saline. Primary endpoints included (1) time to attain three discharge criteria (adequate analgesia, independence from intravenous analgesics, and ambulation ≥ 30 m) and (2) ambulatory distance in 6 min the afternoon after surgery. Patients were discharged with their cLPB and a portable infusion pump, and catheters were removed on the fourth postoperative day.
Results
Patients given 4 days of perineural ropivacaine (n = 24) attained all three discharge criteria in a median (25th-75th percentiles) of 29 (24-45) h, compared with 51 (42-73) h for those of the control group (n = 23; estimated ratio = 0.62; 95% confidence interval, 0.45-0.92;P = 0.011). Patients assigned to receive ropivacaine ambulated a median of 34 (9-55) m the afternoon after surgery, compared with 20 (6-46) m for those receiving normal saline (estimated ratio = 1.3; 95% confidence interval, 0.6-3.0;P = 0.42). Three falls occurred in subjects receiving ropivacaine (13%),versusnone in subjects receiving normal saline.
Conclusions
Compared with an overnight cLPB, a 4-day ambulatory cLPB decreases the time to reach three predefined discharge criteria by an estimated 38% after hip arthroplasty. However, the extended infusion did not increase ambulation distance to a statistically significant degree.
doi:10.1097/ALN.0b013e318182a4a3
PMCID: PMC2590635  PMID: 18719448
21.  The Effects of Varying Local Anesthetic Concentration and Volume on Continuous Popliteal Sciatic Nerve Blocks 
Anesthesia and analgesia  2008;107(2):701-707.
BACKGROUND
It remains unknown whether local anesthetic concentration, or simply total drug dose, is the primary determinant of continuous peripheral nerve block effects. We therefore tested the null hypothesis that providing different concentrations and rates of ropivacaine, but at equal total doses, produces comparable effects when used in a continuous sciatic nerve block in the popliteal fossa.
METHODS
Preoperatively, a perineural catheter was inserted adjacent to the sciatic nerve using a posterior popliteal approach in patients undergoing moderately painful orthopedic surgery at or distal to the ankle. Postoperatively, patients were randomly assigned to receive a perineural ropivacaine infusion of either 0.2% (basal 8 mL/h, bolus 4 mL) or 0.4% (basal 4 mL/h, bolus 2 mL) through the second postoperative day. Therefore, both groups received 16 mg of ropivacaine each hour with a possible addition of 8 mg every 30 min via a patient-controlled bolus dose. The primary end point was the incidence of an insensate limb, considered undesirable, during the 24-h period beginning the morning after surgery. Secondary end points included analgesia and patient satisfaction.
RESULTS
Patients given 0.2% ropivacaine (n = 25) experienced an insensate limb with a mean (sd) of 1.8 (1.8) times, compared with 0.6 (1.1) times for subjects receiving 0.4% ropivacaine (n = 25; estimated difference = 1.2 episodes, 95% confidence interval, 0.3–2.0 episodes; P = 0.009). In contrast, analgesia and satisfaction were similar in each group.
CONCLUSIONS
For continuous popliteal-sciatic nerve blocks, local anesthetic concentration and volume influence block characteristics. Insensate limbs were far more common with larger volumes of relatively dilute ropivacaine. During continuous sciatic nerve block in the popliteal fossa, a relatively concentrated solution in smaller volume thus appears preferable.
doi:10.1213/ane.0b013e3181770eda
PMCID: PMC2585804  PMID: 18633055
22.  The evolution of primary hyperalgesia in orthopedic surgery: quantitative sensory testing and clinical evaluation before and after total knee arthroplasty 
Anesthesia and Analgesia  2007;105(3):815-821.
Background
Quantitative sensory testing (QST), which allows a better characterization of sensory deficits and painful symptoms, may offer additional information on the pathophysiology of postoperative pain.
Methodology
Twenty patients scheduled for total knee anthroplasty were evaluated clinically and with QST before surgery, at one and four days, and at one and four months after surgery. Clinical evaluation included preoperative pain and inflammation of operative knee, postoperative assessment of pain at rest and during movement (Visual Analog Scale score), cumulative morphine consumption, and circumference and temperature of both knees. QST included thermal and mechanical (pressure) pain threshold measurements and assessment of responses to suprathreshold stimuli. Brush-evoked allodynia was also evaluated. Measurements were taken on the operative knee, contra lateral knee, and on the hand as a control site.
Results
All patients had prolonged and severe pain before surgery and inflammation of operative knee. Preoperative OST provided evidence of heat hyperalgesia in the inflammatory area on the operative knee, but absence of punctate or brush-evoked allodynia in the adjacent non inflamed area. Patients had intense postoperative pain, mostly induced by movement. Primary heat hyperalgesia was present on the operative knee on the first and fourth days after surgery, and was associated with punctate mechanical allodynia in the inflammatory area, but not in the adjacent non inflamed area. Postoperative morphine consumption was correlated with preoperative heat hyperalgesia (r=0.63; P=0.01). QST was normalyzed at the 4-month evaluation and only 4 patients had moderate knee pain induced by movement at that time.
Conclusion
Heat hyperalgesia was the predominant OST symptom associated with perioperative pain after total knee arthroplastv and was predictive of postoperative morphine consumption
doi:10.1213/01.ane.0000278091.29062.63
PMCID: PMC2566636  PMID: 17717244
Aged; Analgesia, Patient-Controlled; Analgesics, Opioid; administration & dosage; Arthritis; pathology; physiopathology; surgery; Arthroplasty, Replacement, Knee; Female; Heat; Humans; Hyperalgesia; pathology; physiopathology; Knee; pathology; physiopathology; surgery; Male; Morphine; administration & dosage; Pain Measurement; Pain Threshold; Pain, Postoperative; drug therapy; physiopathology; Postoperative Care; Preoperative Care; Prospective Studies; Severity of Illness Index; Time Factors; Treatment Outcome
23.  The influence of timing of administration on the analgesic efficacy of parecoxib in orthopedic surgery 
Anesthesia and Analgesia  2007;104(6):1521-1527.
Background
Parecoxib, a selective cyclooxygenase-2 inhibitor, may reduce postoperative pain when administered before surgery without increasing bleeding.
Methods
We randomly assigned 62 patients scheduled for total hip arthroplasty to the following intravenous dosing schedule: 1) placebo at induction, at wound closure, and 12 hours after induction (control); 2) parecoxib 40 mg at induction, placebo at wound closure, and parecoxib 40 mg 12 hours after induction (pre); or, 3) placebo at induction, parecoxib 40 mg at wound closure, and parecoxib 40 mg 12 hours after induction (post). Pain scores at rest and with movement recorded every 4 hours for 24 hours using a visual analog scale. Treatment side effects were recorded every 4 hours. Red cell loss for 5 days after surgery was calculated.
Results
Postoperative pain scores were less in pre and post groups than in the control group. Postoperative bleeding was similar in the three groups. There were no significant differences between pre and post groups, nor was their any trend suggesting a pre-emptive analgesic efficacy from preincision administration of parecoxib. Morphine use in the Post Anesthesia Care Unit was reduced in the pre and post groups compared with the control group (14.2±2.0, and 15.7±2.0, versus 20.4±2.3 mg), although the trend was only significant (p < 0.05) in the pre group. The first pain score was also reduced in the pre and post groups compared to the control group (56.1±7.5 and 64.2 ± 7.0 versus 78.3±5), but this was also only significant for the pre group (p=0.001). The delay for first analgesic demand was increased for both the pre and post group compared to the control group (38±9 and 28.2 ± 6.6 versus 18±6 min), but again this was only significant for the pre group (P=0.05). Twenty-four hour consumption of morphine was similar in the pre (26±12 mg) and post groups (25±13 mg); both of which were significantly less than control group (47±27 mg, P<0.001).
Conclusions
Administration of parecoxib before hip arthroplasty did not provide preemptive analgesia. There was a trend towards improved analgesia immediately after surgery with preincision administration, consistent with the expected time course of NSAID drug effect. Perioperative parecoxib administration, consisting of two injections spaced 12 hours apart, improved postoperative analgesia over the first 24 hours without increasing bleeding.
doi:10.1213/01.ane.0000262039.69513.9d
PMCID: PMC2564988  PMID: 17513652
anesthesia; analgesia; parecoxib; preemptive analgesia; coagulation; bleeding; Aged; Analgesia; methods; Arthroplasty, Replacement, Hip; Female; Humans; Isoxazoles; administration & dosage; Male; Middle Aged; Orthopedic Procedures; methods; Pain, Postoperative; drug therapy; epidemiology; Time Factors
24.  Differential effects of antibiotics in combination with G-CSF on survival and polymorphonuclear granulocyte cell functions in septic rats 
Background
In addition to their antimicrobial activity, antibiotics modulate cellular host defence. Granulocyte-colony stimulating factor (G-CSF) is also a well known immunomodulator; however little is known about the interactions of G-CSF with antibiotics. We investigated in septic rats the effects of two antibiotic combinations with G-CSF.
Methods
In two clinic modelling randomised trials (CMRTs), male Wistar rats were anesthetized, given antibiotic prophylaxis, had a laparotomy with peritoneal contamination and infection (PCI), and were randomly assigned (n = 18 rats/group) to: 1) PCI only; 2) PCI+antibiotic; and, 3) PCI+antibiotic+G-CSF prophylaxis (20 μg/kg, three times). This sequence was conducted first with 10 mg/kg coamoxiclav, and then with ceftriaxone/metronidazole (Cef/met, 10/3 mg/kg). In additional animals, the blood cell count, migration and superoxide production of PMNs, systemic TNF-α and liver cytokine mRNA expression levels were determined.
Results
Only the combination coamoxiclav plus G-CSF improved the survival rate (82 vs. 44%, p < 0.001). Improved survival with this combination was accompanied by normalised antimicrobial PMN migratory activity and superoxide production, along with normalised systemic TNF-α levels and a reduced expression of TNF-α and IL-1 in the liver.
Conclusion
There are substantial differences in the interaction of antibiotics with G-CSF. Therefore, the selection of the antibiotic for combination with G-CSF in sepsis treatment should be guided not only by the bacteria to be eliminated, but also by the effects on antimicrobial functions of PMNs and the cytokine response.
doi:10.1186/1471-2334-8-55
PMCID: PMC2386131  PMID: 18447905
25.  Estimation of Mean-body Temperature From Mean-skin and Core Temperature 
Anesthesiology  2006;105(6):1117-1121.
Background: Mean-body temperature (MBT) is the mass-weighted average temperature of body tissues. Core temperature is easy to measure, but direct measurement of peripheral tissue temperature is painful, risky, and requires complex calculations. Alternatively MBT can be estimated from core and mean skin temperatures with a formula proposed by Burton in 1935: MBT = 0.64. TCore + 0.36. TSkin. This formula remains widely used, but not been validated in the perioperative period and seems unlikely to remain accurate in dynamic perioperative conditions such as cardiopulmonary bypass. We thus tested the hypothesis that MBT, as estimated with Burton’s formula, poorly estimates measured MBT at a temperature range between 18 and 36.5° C.
Materials and Methods: We re-evaluated four of our previously published studies in which core and mass-weighted mean peripheral tissue temperatures were measured in patients undergoing substantial thermal perturbations. Peripheral compartment temperatures were estimated using fourth-order regression and integration over volume from 18 intramuscular needle thermocouples, 9 skin temperatures, and "deep" hand and foot temperature. MBT was determined from mass-weighted average of core and peripheral tissue temperatures and estimated from core temperature and mean skin temperature (15 area-weighted sites) using Burton’s formula.
Results: 913 data pairs from 44 study subjects were included in the analysis. Measured MBT ranged from 18 to 36.5°C. There was a remarkably good relationship between measured and estimated MBT: MBTmeasured = 0.94 · MBTestimated + 2.15, r2 = 0.98. Differences between the estimated and measured values averaged -0.09 ± 0.42°C.
Conclusions: We concluded that estimation of MBT from mean skin and core temperatures is generally accurate and precise.
PMCID: PMC1752199  PMID: 17122574

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