Yusuke Kasuya

Anesthetic induction with etomidate, rather than propofol, is associated with increased 30-day mortality and cardiovascular morbidity after noncardiac surgery.

BACKGROUND: Because etomidate impairs adrenal function and blunts the cortisol release associated with surgical stimulus, we hypothesized that patients induced with etomidate suffer greater mortality and morbidity than comparable patients induced with propofol. METHODS: We evaluated the electronic records of 31,148 ASA physical status III and IV patients who had noncardiac surgery at the Cleveland Clinic. Among these, anesthesia was induced with etomidate and maintained with volatile anesthetics in 2616 patients whereas 28,532 were given propofol for induction and maintained with volatile anesthetics. Two thousand one hundred forty-four patients given etomidate were propensity matched with 5233 patients given propofol and the groups compared on 30-day postoperative mortality, length of hospital stay, cardiovascular and infectious morbidities, vasopressor requirement, and intraoperative hemodynamics. RESULTS: Patients given etomidate had 2.5 (98% confidence interval [CI], 1.9–3.4) times the odds of dying than those given propofol. Etomidate patients also had significantly greater odds of having cardiovascular morbidity (odds ratio [OR] [98% CI]: 1.5 [1.2–2.0]), and significantly longer hospital stay (hazard ratio [95% CI]: 0.82 [0.78–0.87]). However, infectious morbidity (OR [98% CI]: 1.0 [0.8–1.2]) and intraoperative vasopressor use (OR [95% CI] 0.92: [0.82–1.0]) did not differ between the agents. CONCLUSION: Etomidate was associated with a substantially increased risk for 30-day mortality, cardiovascular morbidity, and prolonged hospital stay. Our conclusions, especially on 30-day mortality, are robust to a strong unmeasured binary confounding variable. Although our study showed only an association between etomidate use and worse patients’ outcomes but not causal relationship, clinicians should use etomidate judiciously, considering that improved hemodynamic stability at induction may be accompanied by substantially worse longer-term outcomes.

The Correlation Between Bispectral Index and Observational Sedation Scale in Volunteers Sedated with Dexmedetomidine and Propofol

BACKGROUND: Bispectral index (BIS) is a widely used quantitative parameter for evaluating anesthesia and sedation levels. Dexmedetomidine is a novel sedative, providing sedation while patients remain cooperative and can be easily aroused; as a consequence, BIS used with dexmedetomidine may poorly characterize sedation. Thus, we tested the hypothesis that BIS values are lower with dexmedetomidine than with propofol at comparable Observer’s Assessment of Alertness and Sedation (OAA/S) scores. METHODS: This was a randomized, 2-day, crossover study. On the first study day, healthy volunteers were randomly allocated to either propofol or dexmedetomidine sedation. Drugs were administered using computer-controlled infusions targeting an effect-site concentration of 1, 2, and 4 &mgr;g/mL for propofol or a plasma concentration of 0.6, 1.2, and 2.4 ng/mL for dexmedetomidine. The relationship between BIS and OAA/S score was obtained 20 and 40 min after changing each drug concentration. BIS values at each OAA/S score were compared between drugs. The cutoff values of BIS for OAA/S score of ≤2 were obtained by analysis of receiver operating characteristic curves. RESULTS: Nine volunteers were included in our analysis. Heart rates decreased significantly with dexmedetomidine sedation. ETco2 was significantly increased with high doses of propofol but did not increase with high doses of dexmedetomidine. BIS values at OAA/S scores of 1, 2, 3, 4, and 5 during propofol sedation were 95.5 (90-97), 78 (71-84.5), 67 (64-70), 57 (51.5-60), and 34 (30-37), respectively. BIS values at OAA/S scores of 1, 2, 3, 4, and 5 during dexmedetomidine sedation were 95 (79-98), 62 (53.5-68.5), 45.5 (45.3-52), 39.5 (34.3-41.8), and 24.5 (22.5-30.5), respectively. BIS values were significantly less with dexmedetomidine than propofol at OAA/S responsiveness scores of 2, 3, and 4. The calculated cutoff BIS values for OAA/S scores of ≤2 were 67 (sensitivity of 86%, specificity of 97%, and area under the curve of 0.98) for propofol and 46 (sensitivity of 84%, specificity of 91%, and area under the curve of 0.96) for dexmedetomidine. CONCLUSION: The combination of both BIS and sedative scales could provide different and complementary data to the clinician evaluating the patient’s response to sedation than would either tool alone, especially when dexmedetomidine is used.

Learning curves for bag-and-mask ventilation and orotracheal intubation: an application of the cumulative sum method.

Background:In this study, the authors determined the success and failure rates for interns learning bag-and-mask ventilation and orotracheal intubation. Their goal was to determine the amount of experience needed to perform these procedures correctly. Methods:The authors recorded 695 bag-and-mask ventilations and 679 orotracheal intubations performed by 15 inexperienced interns during their 3 month-long anesthesia rotations. Learning curves for each procedure for each intern were constructed with both the standard and risk-adjusted cumulative sum methods. The average number of procedures required to attain a failure rate of 20% was estimated for each technique. Results:Fourteen of 15 interns attained acceptable failure rates at bag-and-mask ventilation after 27 ± 13 procedures, with a median (95% confidence interval) of 25 (15–32) procedures to cross the decision limit when considering all 15 interns. Nine of 15 interns attained acceptable failure rates at orotracheal intubation after 26 ± 8 procedures, with a median of 29 (22–not estimable) procedures to cross the limit when considering all interns. The proportion of interns who attained acceptable failure rates for mask ventilation was greater than for tracheal intubation (93% vs. 60%, P = 0.025). Overall, our interns achieved a bag-and-mask ventilation failure rate of 20% or better after a median of 25 procedures; approximately 80% of interns achieved the goal after 35 procedures or less. Conclusions:Participating interns developed mask ventilation skills faster than orotracheal intubation skills, and there was more variability in the rate at which intubation skills developed. A median of 29 procedures was required to achieve an 80% orotracheal intubation success rate.

Accuracy of postoperative end-tidal Pco2 measurements with mainstream and sidestream capnography in non-obese patients and in obese patients with and without obstructive sleep apnea.

Background:Obtaining accurate end-tidal carbon dioxide pressure measurements via nasal cannula poses difficulties in postanesthesia patients who are mouth breathers, including those who are obese and those with obstructive sleep apnea (OSA); a nasal cannula with an oral guide may improve measurement accuracy in these patients. The authors evaluated the accuracy of a mainstream capnometer with an oral guide nasal cannula and a sidestream capnometer with a nasal cannula that did or did not incorporate an oral guide in spontaneously breathing non-obese patients and obese patients with and without OSA during recovery from general anesthesia. Methods:The study enrolled 20 non-obese patients (body mass index less than 30 kg/m2) without OSA, 20 obese patients (body mass index greater than 35 kg/m2) without OSA, and 20 obese patients with OSA. End-tidal carbon dioxide pressure was measured by using three capnometer/cannula combinations (oxygen at 4 l/min): (1) a mainstream capnometer with oral guide nasal cannula, (2) a sidestream capnometer with a nasal cannula that included an oral guide, and (3) a sidestream capnometer with a standard nasal cannula. Arterial carbon dioxide partial pressure was determined simultaneously. The major outcome was the arterial-to-end-tidal partial pressure difference with each combination. Results:In non-obese patients, arterial-to-end-tidal pressure difference was 3.0 ± 2.6 (mean ± SD) mmHg with the mainstream capnometer, 4.9 ± 2.3 mmHg with the sidestream capnometer and oral guide cannula, and 7.1 ± 3.5 mmHg with the sidestream capnometer and a standard cannula (P < 0.05). In obese non-OSA patients, it was 3.9 ± 2.6 mmHg, 6.4 ± 3.1 mmHg, and 8.1 ± 5.0 mmHg, respectively (P < 0.05). In obese OSA patients, it was 4.0 ± 3.1 mmHg, 6.3 ± 3.2 mmHg, and 8.3 ± 4.6 mmHg, respectively (P < 0.05). Conclusions:Mainstream capnometry performed best, and an oral guide improved the performance of sidestream capnometry. Accuracy in non-obese and obese patients, with and without OSA, was similar.

Early Postoperative Subcutaneous Tissue Oxygen Predicts Surgical Site Infection

BACKGROUND:Subcutaneous oxygen partial pressure is one of several determinants of surgical site infections (SSIs). However, tissue partial pressure is difficult to measure and requires invasive techniques. We tested the hypothesis that early postoperative tissue oxygen saturation (StO2) measured with near-infrared spectroscopy predicts SSI. METHODS:We evaluated StO2 in 116 patients undergoing elective colon resection. Saturation was measured near the surgical incision, at the upper arm, and at the thenar muscle with an InSpectra™ tissue spectrometer model 650 (Hutchinson Technology Inc., Hutchinson, MN) 75 minutes after the end of surgery and on the first postoperative day. An investigator blinded to StO2 assessed patients daily for wound infection. Receiver operating characteristic curves were used to analyze the performance of StO2 measurements as a predictor of SSI. RESULTS:In 23 patients (≈20%), SSI was diagnosed 9 ± 5 days (mean ± SD) after surgery. Patients who did and did not develop an SSI had similar age (48 ± 14 vs 48 ± 15 years, respectively; P = 0.97) and gender (female:male, 15:8 vs 46:47, respectively), but patients who developed SSI weighed more (body mass index 32 ± 7 vs 27 ± 6 kg/m2; P < 0.01). StO2 at the upper arm was lower in patients who developed SSI than in those who did not develop SSI (52 ± 22 vs 66 ± 21; P = 0.033), and these measurements had a sensitivity of 71% and specificity of 60% for predicting SSI, using StO2 of 66% as the cutoff point. CONCLUSION:StO2 measured at the upper arm only 75 minutes after colorectal surgery predicted development of postoperative SSI, although the infections were typically diagnosed more than a week later. Although further testing is required, StO2 measurements may be able to predict SSI and thus allow earlier preventive measures to be implemented.

Suppression of shivering during hypothermia using a novel drug combination in healthy volunteers.

Background:Hypothermia may be beneficial in stroke victims; however, it provokes vigorous shivering. Buspirone and dexmedetomidine each linearly reduce the shivering threshold with minimal sedation and no respiratory depression. This study tested the hypotheses that the combination of buspirone and dexmedetomidine would (1) synergistically reduce the shivering threshold, (2) synergistically reduce the gain and maximum intensity of shivering, and (3) produce sufficient inhibition to permit cooling to 34°C without excessive hypotension or sedation. Methods:Eight healthy men were randomly assigned on 4 days to (1) no drug, (2) buspirone (60 mg orally), (3) dexmedetomidine (intravenous infusion to target plasma concentration of 0.6 ng/ml), or (4) combination of buspirone and dexmedetomidine at same doses. Lactated Ringers solution (approximately 3°C) was infused intravenously to decrease tympanic membrane temperature by 1.5°C/h. Shivering threshold was defined as an increase in oxygen consumption greater than 20%. Sedation was evaluated using the Observers Assessment of Sedation/Alertness scale. Results:Mean arterial pressure and heart rate were slightly lower on dexmedetomidine and combination days. Likewise, the level of sedation was statistically different on these 2 days but clinically unimportant. Buspirone reduced the shivering threshold from 36.6°C ± 0.4°C to 35.9°C ± 0.4°C, dexmedetomidine reduced it to 34.7°C ± 0.5°C, and the combination to 34.1 ± 0.4°C. The interaction effect of 0.04°C was not significant. The gain of shivering and maximum shivering intensity were similar on each day. Conclusions:The combination of buspirone and dexmedetomidine additively reduced the shivering threshold. Thus, supplementing dexmedetomidine with buspirone blocks shivering and causes only minimal sedation.

Ventilator-associated pneumonia in critically ill stroke patients: Frequency, risk factors, and outcomes ☆,☆☆

PURPOSE Our main objective was to assess incidence, risk factors, and outcomes of ventilator-associated pneumonia (VAP) in stroke patients. MATERIALS AND METHODS After obtaining approval from the Human Studies Committee, we reviewed the electronic records from our intensive care unit database of 111 stroke patients on mechanical ventilation for more than 48 hours. Thirty-six risk factors related to disease and general health status, and 8 related to care-all assigned a priori-were collected and analyzed. Selected factors with univariate statistical significance (P < .05) were then analyzed with multivariate logistic regression. RESULTS Thirty-one patients developed pneumonia (28%). Methicillin-resistant Staphylococcus aureus (n = 12) and methicillin-sensitive S aureus (n = 7) were the most common pathogenic bacteria. Chronic lung disease, neurological status at admission as assessed by the National Institutes of Health Stroke Scale, and hemorrhagic transformation were the independent risk factors contributing to VAP. Worsening oxygenation index (arterial partial pressure of oxygen/fraction of inspired oxygen) and proton pump inhibitor use for ulcer prophylaxis were other potentially important factors. CONCLUSIONS Pneumonia appears as a frequent problem in mechanically ventilated stroke patients. Chronic lung disease history, severity of stroke level at admission, and hemorrhagic transformation of stroke set the stage for developing VAP. The duration of both mechanical ventilation and intensive care unit stay gets significantly prolonged by VAP, but it does not affect mortality.

Effects of Dexmedetomidine and Propofol on Lower Esophageal Sphincter and Gastroesophageal Pressure Gradient in Healthy Volunteers

Background:Many anesthetics reduce lower esophageal sphincter pressure (LESP). Reduced pressure and consequent reduction in the gastroesophageal pressure gradient (GEPG) thus promotes gastroesophageal reflux and may contribute to aspiration pneumonia and associated morbidity. Therefore, the authors compared LESP and GEPG during dexmedetomidine and propofol sedation. Methods:Using a randomized, double-blind, crossover design, 11 healthy volunteers were sedated on 2 separate days. Baseline LESP and GEPG were recorded each day. Subsequently, on each day volunteers received three 40-min-long sedative infusions of increasing doses of 0.6, 1.2, and 2.4 ng/ml dexmedetomidine or 1, 2, and 4 &mgr;g/ml propofol. LESP and GEPG were recorded during inhalation and expiration at 20 and 40 min after starting each infusion phase, and these measurements were averaged. Results are presented as mean (95% confidence interval). Results:Two subjects did not return for the dexmedetomidine study day, and the dexmedetomidine results were unusable in another; propofol results in these volunteers were nonetheless retained for analysis. There were no significant differences in LESP and GEPG as a function of drug. However, there was a small but significant 7.4 (−1.6 to −13.2) mmHg (approximately 25%) dose-dependent decrease in LESP over the range of targeted low to high blood levels of each drug. Conclusions:Both dexmedetomidine and propofol have similar effects on LESP and GEPG. Although both of the drugs cause some decrease in LESP at high concentrations, it is unlikely that this effect would promote gastroesophageal reflux during sedation.

The effect of aminophylline on loss of consciousness, bispectral index, propofol requirement, and minimum alveolar concentration of desflurane in volunteers.

BACKGROUND: Adenosine is a soporific neuromodulator; aminophylline, which is clinically used as a bronchodilator, antagonizes the action of adenosine in the central nervous system. Thus, we tested the hypothesis that aminophylline delays loss of consciousness (LOC) and speeds recovery of consciousness (ROC) with propofol anesthesia, and that aminophylline increases the minimum alveolar concentration (MAC) of desflurane. METHODS: In this double-blind crossover study, volunteers were randomized to either aminophylline or saline on different days. Aminophylline 6 mg/kg was given IV, followed by 1.5 mg · kg−1 · h−1 throughout the study day. After 1 h of aminophylline or saline administration, propofol 200 mg was given at a rate of 20 mg/min. The bispectral index was continuously monitored, as were times to LOC and ROC. After recovery from propofol, general anesthesia was induced with sevoflurane and subsequently maintained with desflurane. The Dixon “up-and-down” method was used to determine MAC in each volunteer after repeated tetanic electrical stimulation. RESULTS: Eight volunteers completed both study days. Time to LOC was prolonged by aminophylline compared with saline (mean ± sd) (7.7 ± 2.03 min vs 5.1 ± 0.75 s, respectively, P = 0.011). The total propofol dose at LOC was larger with aminophylline (2.2 ± 0.9 vs 1.4 ± 0.4 mg/kg, P = 0.01), and the time to ROC was shorter (6.18 ± 3.96 vs 12.2 ± 4.73 min, P = 0.035). The minimum bispectral index was greater with aminophylline (51 ± 15 vs 38 ± 9, P = 0.034). There was no difference in MAC. CONCLUSION: Aminophylline decreases the sedative effects of propofol but does not affect MAC of desflurane as determined by tetanic electrical stimulation.

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.