Association between Intraoperative Hypotension and Hypertension and 30-day Postoperative Mortality in Noncardiac Surgery.

BACKGROUND: Although deviations in intraoperative blood pressure are assumed to be associated with postoperative mortality, critical blood pressure thresholds remain undefined. Therefore, the authors estimated the intraoperative thresholds of systolic blood pressure (SBP), mean blood pressure (MAP), and diastolic blood pressure (DBP) associated with increased risk-adjusted 30-day mortality. METHODS: This retrospective cohort study combined intraoperative blood pressure data from six Veterans Affairs medical centers with 30-day outcomes to determine the risk-adjusted associations between intraoperative blood pressure and 30-day mortality. Deviations in blood pressure were assessed using three methods: (1) population thresholds (individual patient sum of area under threshold [AUT] or area over threshold 2 SDs from the mean of the population intraoperative blood pressure values), (2). absolute thresholds, and (3) percent change from baseline blood pressure. RESULTS: Thirty-day mortality was associated with (1) population threshold: systolic AUT (odds ratio, 3.3; 95% CI, 2.2 to 4.8), mean AUT (2.8; 1.9 to 4.3), and diastolic AUT (2.4; 1.6 to 3.8). Approximate conversions of AUT into its separate components of pressure and time were SBP < 67 mmHg for more than 8.2 min, MAP < 49 mmHg for more than 3.9 min, DBP < 33 mmHg for more than 4.4 min. (2) Absolute threshold: SBP < 70 mmHg for more than or equal to 5 min (odds ratio, 2.9; 95% CI, 1.7 to 4.9), MAP < 49 mmHg for more than or equal to 5 min (2.4; 1.3 to 4.6), and DBP < 30 mmHg for more than or equal to 5 min (3.2; 1.8 to 5.5). (3) Percent change: MAP decreases to more than 50% from baseline for more than or equal to 5 min (2.7; 1.5 to 5.0). Intraoperative hypertension was not associated with 30-day mortality with any of these techniques. CONCLUSION: Intraoperative hypotension, but not hypertension, is associated with increased 30-day operative mortality.

A randomized, open-label study of the safety and tolerability of fospropofol for patients requiring intubation and mechanical ventilation in the intensive care unit.

BACKGROUND: Current drugs for induction and maintenance of sedation in mechanically ventilated patients in the intensive care unit have limitations. Fospropofol, a prodrug of propofol, has not been studied as a sedative in the ICU setting. METHODS: In this randomized, open-label pilot study, patients received 1 of 3 regimens with a goal of maintaining a Ramsay Sedation Score of 2 to 5: (1) fospropofol IV infusion with a bolus and increased infusion rate for agitation events (infusion/bolus); (2) fospropofol IV infusion with an increased infusion rate for agitation events (infusion only); or (3) propofol IV infusion with an increased infusion rate for agitation events. RESULTS: Sixty patients received study drug and were included in the safety and efficacy analyses. Because incidence rates for adverse events were similar between fospropofol groups, and because the study was not powered to determine significant differences between treatment groups for safety variables, adverse events for both fospropofol groups were combined. In the fospropofol groups, 28 out of 38 patients (74%) experienced treatment-emergent adverse events in comparison with 14 out of 22 patients (64%) in the propofol group. The most common treatment-emergent adverse events with fospropofol were procedural pain (21.1%) and nausea (13.2%). Two patients (1 each in the fospropofol infusion/bolus and the propofol groups) experienced hypotension during the study as a potential sedation-related adverse event. Mean plasma formate levels were not significantly different among groups. Patients in all 3 treatment groups maintained Ramsay Sedation Scores of 2 to 5 for >90% of the time they were sedated. CONCLUSION: This pilot study suggests that fospropofol, administered in either an infusion/bolus or infusion-only regimen, is tolerable and effective for short-term induction and maintenance of sedation in mechanically ventilated intensive care unit patients.

ICU sedation after coronary artery bypass graft surgery: dexmedetomidine-based versus propofol-based sedation regimens.

OBJECTIVE: To compare dexmedetomidine-based to propofol-based sedation after coronary artery bypass graft (CABG) surgery in the intensive care unit (ICU). DESIGN: Randomized, open label. SETTING: Twenty-five centers in the United States and Canada. PARTICIPANTS: Two hundred ninety-five adults undergoing CABG surgery. INTERVENTIONS: At sternal closure, patients in group A received 1.0 microg/kg of dexmedetomidine over 20 minutes and then 0.2 to 0.7 microg/kg/h to maintain a Ramsay sedation score > or =3 during assisted ventilation and > or =2 after extubation. Patients could be given propofol for additional sedation if necessary; group B patients received propofol-based care according to each investigator's standard practice. MEASUREMENTS AND MAIN RESULTS: Mean sedation levels were within target ranges in both groups. Mean times to weaning and extubation were similar, although fewer dexmedetomidine patients remained on the ventilator beyond 8 hours. Morphine use was significantly reduced in the dexmedetomidine group. Only 28% of the dexmedetomidine patients required morphine for pain relief while ventilated versus 69% of propofol-based patients (p < 0.001). Propofol patients required 4 times the mean dose of morphine while in the ICU. Mean blood pressure increased initially in both groups, then decreased to 3 mmHg below baseline in dexmedetomidine patients; mean arterial pressure remained at 9 mmHg above baseline in propofol patients. No ventricular tachycardia occurred in the dexmedetomidine-sedated patients compared with 5% of the propofol patients (p = 0.007). Respiratory rates and blood gases were similar. Fewer dexmedetomidine patients received beta-blockers (p = 0.014), antiemetics (p = 0.015), nonsteroidal anti-inflammatory drugs (p < 0.001), epinephrine (p = 0.030), or high-dose diuretics (p < 0.001). CONCLUSION: Dexmedetomidine provided safe and effective sedation for post-CABG surgical patients and significantly reduced the use of analgesics, beta-blockers, antiemetics, epinephrine, and diuretics.

Tracheoscopy with the rapiscope to verify endotracheal tube placement.

STUDY OBJECTIVE: To determine whether tracheoscopy is an accurate and quick method for verifying correct placement of the tracheal tube after intubation. DESIGN: Prospective, randomized study. SETTING: Operating rooms of a teaching hospital. PATIENTS: 26 patients scheduled for surgery and general anesthesia. INTERVENTIONS: 8.0-mm tracheal tubes were inserted into both the trachea and the esophagus. Tracheoscopy was performed consecutively through both tracheal tubes by a variety of clinicians. MEASUREMENTS: The times taken to correctly identify the trachea and the esophagus were recorded. MAIN RESULTS: Correct identification of either the esophagus or the trachea occurred with a 100% sensitivity and a 96% specificity. The mean time to recognize either the trachea or the esophagus was 22.0 seconds. CONCLUSIONS: Tracheoscopy is a reliable method for quickly verifying proper endotracheal placement of a tracheal tube.

The role of the alpha2-adrenoceptor agonist dexmedetomidine in postsurgical sedation in the intensive care unit.

Dexmedetomidine was evaluated for sedation of 401 post-surgical patients in this double-blind, randomized, placebo-controlled, multicenter trial. Dexmedetomidine or saline was started on arrival in the intensive care unit (ICU) (1.0 mcg/kg for 10 minutes), then titrated at 0.2 to 0.7 mcg/kg/h to effect. Patients could be given propofol if necessary. Morphine was administered for pain. Sixty percent of the dexmedetomidine patients required no other sedative to maintain an RSS > or = 3; 21% required < 50 mg propofol. In contrast, 76% of the control group received propofol; 59% required > or = 50 mg. Dexmedetomidine patients required significantly less morphine for pain relief (P <.001). Continuously given throughout the ICU stay, dexmedetomidine had no effect on respiratory rate, oxygen saturation, duration of weaning, or times to extubation. Nurses judged the dexmedetomidine patients were easier to manage. Later, fewer dexmedetomidine patients remembered pain or discomfort. The majority of dexmedetomidine patients maintained blood pressures within normal range, without rebound. Hypertension, atelectasis, and rigors occurred more frequently in the control group, while hypotension and bradycardia occurred more frequently in the dexmedetomidine group. Preoperative cardiovascular conditions were not risk factors for dexmedetomidine patients.

Severe methemoglobinemia on reexposure to benzocaine.

We report a 65-year-old male who developed severe methemoglobinemia only on reexposure to benzocaine. The patient needed two awake fiberoptic intubations for emergency surgeries. On the second exposure, the patient was septic and malnourished, and he was taking acetaminophen. He developed a methemoglobin level of 55%. Possible reasons for the methoglobinemia on reexposure are discussed in this report.

Carbon dioxide homeostasis during transperitoneal or extraperitoneal laparoscopic pelvic lymphadenectomy: a real-time intraoperative comparison.

The primary goal of this study was to evaluate differences in carbon dioxide metabolism between patients undergoing transperitoneal or extraperitoneal laparoscopic pelvic lymph node dissection (L-PLND) for staging of adenocarcinoma of the prostate (CaP). Eighteen candidates undergoing L-PLND were divided between the transperitoneal (N = 12) and extraperitoneal (N = 6) approaches. End-tidal partial pressure of CO2 (PeCO2) and minute volume of expired CO2 (VCO2) were considered indicators of CO2 absorption. These two parameters were monitored intraoperatively utilizing a metabolic cart and Ohmeda Rascal-II. The cardiostimulatory effect of increasing serum CO2 and the ventilatory countermeasures used to correct the iatrogenic hypercapnia associated with CO2 insufflation were also measured. With the exception of the region of CO2 insufflation, the operative procedure and perioperative care were identical for the two groups. Preoperative patient characteristics were similar. The mean time of CO2 insufflation was 136 minutes for the transperitoneal group and 120 minutes for the extraperitoneal group. The absorption of CO2 was significantly greater and more rapid during extraperitoneal L-PLND. This may be attributable to more profound CO2 absorption from the parietal peritoneal surface compounded by subcutaneous CO2 emphysema. Disruption of microvascular and lymphatic channels during the development of the extraperitoneal working space facilitates direct CO2 absorption into the intravascular space. A minor increase in heart rate and systolic blood pressure was noted during CO2 insufflation. In all but one patient (extraperitoneal group), hypercarbia and acidemia were prevented by an increased ventilatory rate. The potential dysrhythmogenicity of hypercarbia may contraindicate the extraperitoneal approach in patients with cardiopulmonary disease.

The interactions of midazolam and flumazenil on human memory and cognition.

BACKGROUND: Previous research has been unable to show unequivocally whether flumazenil can reverse completely, partially, or not at all the memory effects of benzodiazepines. The effects of midazolam on implicit memory are also unknown. The behavioral effects of flumazenil by itself, and the acute reversal of benzodiazepine effects, are also controversial. The current study was designed to investigate these questions. METHODS: Using a prospective randomized, double-blind crossover study design, memory was assessed using both direct (free recall and recognition) and indirect (word completion) measures. Other cognitive effects were assessed using the digit symbol substitution task. Sedation and other mood effects were assessed using subjective rating scales. Seventy-two healthy subjects were assigned to three equal groups according to the dose of midazolam received (0, 0.05, and 0.1 mg/kg). Each subject received varying doses of flumazenil (0, 1, and 3 mg) in three sessions, at least 1 week apart. After baseline administration of the tasks, midazolam was administered. The assessments were repeated 20 min later, followed by administration of flumazenil. The assessments were repeated 5 and 30 min after administration of flumazenil. After a 2-h recovery period, delayed memory tests were given. RESULTS: Both doses of midazolam decreased all scores in the memory and digit symbol substitution tests and mood ratings. Flumazenil reversed both the sedative and the memory effects of the benzodiazepine. The reversal was as complete with the 1-mg dose of flumazenil as with the 3-mg dose. Flumazenil by itself, and the acute reversal of midazolam effects, caused no significant behavioral reactions. CONCLUSIONS: Midazolam impairs explicit and implicit memory. Flumazenil reverses both the sedative and memory effects of the drug. Flumazenil, in the doses used, has no intrinsic actions.

The effect of hemodialysis on protein metabolism. A leucine kinetic study.

To assess the effect of hemodialysis on protein metabolism, leucine flux was measured in seven patients before, during, and after high efficiency hemodialysis using cuprophane dialyzers and bicarbonate dialysate during a primed-constant infusion of L-[1-13C]leucine. The kinetics [mumol/kg per h, mean +/- SD] are as follows: leucine appearance into the plasma leucine pool was 86 +/- 28, 80 +/- 28, and 85 +/- 25, respectively, before, during, and after dialysis. Leucine appearance into the whole body leucine pool, derived from plasma [1-13C]alpha-ketoisocaproate enrichment, was 118 +/- 31, 118 +/- 31, and 114 +/- 28 before, during, and after dialysis, respectively. In the absence of leucine intake, appearance rate reflects protein degradation, which was clearly unaffected by dialysis. Leucine oxidation rate was 17.3 +/- 7.8 before, decreased to 13.8 +/- 7.8 during, and increased to 18.9 +/- 10.3 after dialysis (P = 0.027). Leucine protein incorporation was 101 +/- 26 before, was reduced to 89 +/- 23 during, and returned to 95 +/- 23 after dialysis (P = 0.13). Leucine net balance, the difference between leucine protein incorporation and leucine release from endogenous degradation, was -17.3 +/- 7.8 before, decreased to -28.5 +/- 11.0 during, and returned to -18.9 +/- 10.3 after dialysis (P < 0.0001). This markedly more negative leucine balance during dialysis was accountable by dialysate leucine loss, which was 14.4 +/- 6.2 mumol/kg per h. These data suggest that hemodialysis using a cuprophane membrane did not acutely induce protein degradation. It was, nevertheless, a net catabolic event because protein synthesis was reduced and amino acid was lost into the dialysate.

The effect of respiratory alkalosis on oxygen consumption in anesthetized patients.

STUDY OBJECTIVE: To investigate whether hyperventilation significantly altered oxygen consumption in anesthetized and paralyzed patients undergoing surgery. DESIGN: Open crossover trial with 1 hour of hyperventilation preceded and followed by 1 hour of normoventilation. SETTING: University medical center. PATIENTS: Eight patients (five men and three women) undergoing lengthy orthopedic surgery with general anesthesia and muscle paralysis. INTERVENTIONS: After baseline normoventilation for 1 hour (Period 1), the anesthetized patients were hyperventilated to an arterial carbon dioxide tension (PaCO2) of 20 to 25 mmHg for 1 hour (Period 2). Patients then experienced another hour of normoventilation (Period 3). MEASUREMENTS AND MAIN RESULTS: Hemodynamic variables, electrocardiography, temperature, end-tidal partial pressure of CO2 (PETCO2), oxygen consumption (VO2), carbon dioxide production, and minute ventilation were continuously followed throughout the study, and arterial blood gases were drawn at the beginning and end of each study period. During the period of hyperventilation, pH was significantly higher and P.ETCO2 and PaCO2 significantly lower compared with the periods of normoventilation. VO2 was significantly increased during hyperventilation compared with the periods of normoventilation. Hemodynamic variables and temperature were similar in the three study periods. CONCLUSIONS: In anesthetized paralyzed patients, there is an increase in whole-body VO2 with hypocapnic alkalosis.

Accuracy of the FEF CO2 detector in the assessment of endotracheal tube placement.

The sensitivity and reliability of the FEF end-tidal CO2 detector were investigated for its suitability in the assessment of correct placement of an endotracheal tube. Sensitivity was determined by having eight blinded volunteers observe the color change in the FEF detector with the administration of different volumes and varying CO2 concentrations of gas mixture. The color change in the FEF detector was also assessed during esophageal ventilations before and after administration of carbonated beverage into the stomach of swine and during cardiopulmonary resuscitation in swine. An interpersonal variation was present among the blinded observers during the color-matching process. Different colors were observed with the same volume and CO2 concentration of gas mixture. During esophageal ventilations before or after the administration of carbonated beverage, the FEF detector was neither accurate nor rapid in identifying esophageal placement of the endotracheal tube. The "C" color was displayed during the initial six ventilations in one swine, and esophageal intubation would have been missed. The FEF detector could (by displaying a "C" color) identify one of six correctly intubated swine during cardiopulmonary resuscitation. In conclusion, the FEF CO2 detector does not have the characteristics to reliably assess the correct placement of an endotracheal tube.

Efficacy of therapeutic suggestions for improved postoperative recovery presented during general anesthesia.

There have been claims that the postoperative course of patients may be improved by presentation during general anesthesia of therapeutic suggestions which predict a rapid and comfortable postoperative recovery. This study evaluated the effectiveness of such therapeutic suggestions under double-blind and randomized conditions. A tape recording predicting a smooth recovery during a short postoperative stay without pain, nausea, or vomiting was played during anesthesia to about half the patients (N = 109), while the remaining, control patients were played a blank tape instead (N = 100). The patients were primarily undergoing operations on the fallopian tubes, total abdominal hysterectomy, vertical banding gastroplasty, cholecystectomy, and ovarian cystectomy or myomectomy. The anesthesia methods consisted of either isoflurane with 70% nitrous oxide in oxygen to produce end-tidal concentrations of 1.0, 1.3, or 1.5 MAC; or 70% nitrous oxide in oxygen combined with high or low doses of opioids. Assessments of the efficacy of the therapeutic suggestions in the recovery room and throughout the postoperative hospital stay included: the frequency of administration of analgesic and antiemetic drugs; opioid doses; the incidence of fever; nausea, retching, and vomiting; other gastrointestinal and urinary symptoms; ratings of pain; ratings of anxiety; global ratings of the patients' physical and psychological recoveries by the patients and their nurses; and length of postoperative hospital stay. There were no meaningful, significant differences in postoperative recovery of patients receiving therapeutic suggestions and controls. These negative results were not likely to be due to insensitivity of the assessments of recovery, as they showed meaningful interrelations among themselves and numerous differences in recovery following different types of surgery. Widespread utilization of therapeutic suggestions as a routine operating room procedure seems premature in the absence of adequate replication of previously published positive studies.

Reliability of capnography in identifying esophageal intubation with carbonated beverage or antacid in the stomach.

To evaluate the reliability of capnography in identifying esophageal intubation in the presence of a carbonated beverage in the stomach, we first investigated the amount of CO2 released from different carbonated beverages and antacids in a simulated stomach; next we measured the end-expired CO2 level during esophageal ventilation with a carbonated beverage in the stomachs of six swine. CO2 levels of approximately 20% were consistently observed in all carbonated beverages. The CO2 levels obtained with sodium bicarbonate, Maalox, and sodium citrate were 19.3%, 2.0%, and 0%, respectively. CO2 waveforms were observed during esophageal ventilation in five of six animals after intragastric administration of a carbonated beverage. An end-expired CO2 level of 2.5% or more was observed in two swine. The highest end-expired CO2 level measured was 5.3%. We conclude that although capnography is convenient and effective, it lacks all the attributes of an ideal monitor for detecting esophageal intubation.

Stable and reproducible porcine model of acute lung injury induced by oleic acid.

BACKGROUND AND METHODS: Previous studies on acute lung injury induced with oleic acid did not attempt to limit the influence of secondary changes on pulmonary circulation, and cardiopulmonary variable data were only collected and processed intermittently. Our study was designed to continuously monitor the following variables in five swine: systemic and pulmonary pressure; mixed venous oxygen saturation (SVO2) and arterial oxygen saturation (SaO2); minute oxygen consumption and CO2 production before, during, and for 4 hr after the infusion of oleic acid. A personal computer was programmed to produce 20-sec updates of deadspace ratio (VD/VT), venous admixture (Qsp/Qt), pulmonary (PVR) and systemic vascular resistance (SVR), and cardiac output (Qt) from these data. RESULTS: During the oleic acid infusion, there were increases in PVR, SVR, heart rate (HR), mean pulmonary arterial pressure (MPAP), Qsp/Qt, and VD/VT, and a decrease in Qt, SaO2, and SVO2. Thirty minutes after the oleic acid infusion, there was a further increase in HR, Qsp/Qt, and VD/VT, while MPAP, PVR, and SVR gradually decreased to pre-oleic acid infusion levels. No further decrease in SaO2, SVO2, and Qt was observed during that time. After the 30-min period, there was no further change in the cardiopulmonary variables. CONCLUSION: Our method of continuous monitoring was able to demonstrate in swine both the dynamic changes during, and stability after, the oleic acid infusion.

Human learning during general anaesthesia and surgery.

To determine if learning occurs during general anaesthesia, 72 women undergoing surgery were given postoperative implicit memory tests in which performance could be influenced by auditory information presented during general anaesthesia. Two methods of anaesthesia were used: nitrous oxide and opioids (n = 24) or nitrous oxide and isoflurane (1, 1.3 and 1.5 MAC for n = 12, 24 and 12, respectively). Three tests showed some retention, apparently unconscious, of information presented during anaesthesia: in Behavioural Suggestions tests, patients who were instructed during anaesthesia to touch a particular body part (ear or nose) during later questioning touched the "correct" (suggested) body part longer than the "incorrect" (not suggested) body part during a postoperative interview on the day of surgery (means 2.5 vs 0.2 s); in World Completion tests, patients shown a page containing the first three letters of words and asked to give words beginning with those letters gave more words from a list that had been played during anaesthesia than from a list not played (means 0.48 vs 0.27 words); in Nonsense Word tests, patients who were played different nonsense words between two and 16 times during anaesthesia preferred and guessed more accurately those that had been played most often (16 times) relative to those played less often in subsequent preference and recognition tests (means 56% vs 46% for preference and 62% vs 48% for recognition), while showing no such patterns in additional control tests. Learning did not vary with the method of anaesthesia, as might have been expected if learning was a monotonic function of brain depression. Some information processing functions of the brain evidently continue to function during adequate general anaesthesia.

A comparative study of methods of detection of esophageal intubation.

The trachea and esophagus of 21 patients were simultaneously intubated to comparatively evaluate methods for detecting esophageal intubation. In succession, the trachea and esophagus were ventilated with the same inspiratory volume of 621 +/- 45 mL (mean +/- SD). Carbon dioxide (CO2) levels, volumes, and temperatures of expired gas were measured from the tracheal and esophageal tubes. End-expired CO2 levels of gases from the trachea and esophagus were 4.9 +/- 0.7% and 0.6 +/- 0.6%, respectively, with CO2 waveforms observed in 7 (33%) patients with esophageal intubations. Volumes expired from the tracheal tube averaged 615 +/- 64 mL and from the esophageal tube 35 +/- 16 mL (P less than 0.001). Peak temperatures of expired gas recorded from the tracheal tube (32.0 +/- 0.73 degrees C) were higher than those from the esophageal tube (27.3 +/- 1.2 degrees C) (P less than 0.001). The shape of temperature waveforms with a correctly placed tracheal tube remained constant with each ventilation, contrary to that obtained from an esophageal tube. Although the occasional detected of CO2 waveforms from an esophageal tube might lead to an incorrect assessment of tube placement, this limitation of CO2 analyzer can be offset by measurement of volume and temperature of expired gas in identifying placement of an endotracheal tube.