Inhaled nitric oxide for the early treatment of persistent pulmonary hypertension of the term newborn: a randomized, double-masked, placebo-controlled, dose-response, multicenter study. The I-NO/PPHN Study Group.

OBJECTIVES: To assess the dose-related effects of inhaled nitric oxide (I-NO) as a specific adjunct to early conventional therapy for term infants with persistent pulmonary hypertension (PPHN), with regard to neonatal outcome, oxygenation, and safety. METHODS: Randomized, placebo-controlled, double-masked, dose-response, clinical trial at 25 tertiary centers from April 1994 to June 1996. The primary endpoint was the PPHN Major Sequelae Index ([MSI], including the incidence of death, extracorporeal membrane oxygenation (ECMO), neurologic injury, or bronchopulmonary dysplasia [BPD]). Patients required a fraction of inspired oxygen [FIO2] of 1.0, a mean airway pressure >/=10 cm H2O on a conventional ventilator, and echocardiographic evidence of PPHN. Exogenous surfactant, concomitant high-frequency ventilation, and lung hypoplasia were exclusion factors. Control (0 ppm) or nitric oxide (NO) (5, 20, or 80 ppm) treatments were administered until success or failure criteria were met. Due to slowing recruitment, the trial was stopped at N = 155 (320 planned). RESULTS: The baseline oxygenation index (OI) was 24 +/- 9 at 25 +/- 17 hours old (mean +/- SD). Efficacy results were similar among NO doses. By 30 minutes (no ventilator changes) the PaO2 for only the NO groups increased significantly from 64 +/- 39 to 109 +/- 78 Torr (pooled) and systemic arterial pressure remained unchanged. The baseline adjusted time-weighted OI was also significantly reduced in the NO groups (-5 +/- 8) for the first 24 hours of treatment. The MSI rate was 59% for the control and 50% for the NO doses (P = .36). The ECMO rate was 34% for control and 22% for the NO doses (P = .12). Elevated methemoglobin (>7%) and nitrogen dioxide (NO2) (>3 ppm) were observed only in the 80 ppm NO group, otherwise no adverse events could be attributed to I-NO, including BPD. CONCLUSION: For term infants with PPHN, early I-NO as the sole adjunct to conventional management produced an acute and sustained improvement in oxygenation for 24 hours without short-term side effects (5 and 20 ppm doses), and the suggestion that ECMO use may be reduced.

Safety of withdrawing inhaled nitric oxide therapy in persistent pulmonary hypertension of the newborn.

OBJECTIVE: Because of case reports describing hypoxemia on withdrawal of inhaled nitric oxide (I-NO), we prospectively examined this safety issue in newborns with persistent pulmonary hypertension who were classified as treatment successes or failures during a course of I-NO therapy. METHODS: Randomized, placebo-controlled, double-masked, dose-response clinical trial at 25 tertiary centers from April 1994 to June 1996. Change in oxygenation and outcome (death and/or extracorporeal membrane oxygenation) during or immediately after withdrawing I-NO were the principal endpoints. Patients (n = 155) were term infants, <3 days old at study entry with echocardiographic evidence of persistent pulmonary hypertension of the newborn. Exclusion criteria included previous surfactant treatment, high-frequency ventilation, or lung hypoplasia. Withdrawal from treatment gas (0, 5, 20, or 80 ppm) started once treatment success or failure criteria were met. Withdrawal of treatment gas occurred at 20% decrements at <4 hours between steps. RESULTS: The patient profile was similar for placebo and I-NO groups. Treatment started at an oxygenation index (OI) of 25 +/- 10 (mean +/- SD) at 26 +/- 18 hours after birth. For infants classified as treatment successes (mean duration of therapy = 88 hours, OI <10), decreases in the arterial partial pressure of oxygen (PaO(2)) were observed only at the final step of withdrawal. On cessation from 1, 4, and 16 ppm, patients receiving I-NO demonstrated a dose-related reduction in PaO(2) (-11 +/- 23, -28 +/- 24, and -50 +/- 48 mm Hg, respectively). For infants classified as treatment failures (mean duration of therapy = 10 hours), no change in OI occurred for the placebo group (-13 +/- 36%, OI of 31 +/- 11 after the withdrawal process); however a 42 +/- 101% increase in OI to 46 +/- 21 occurred for the pooled nitric oxide doses. One death was possibly related to withdrawal of I-NO. CONCLUSION: For infants classified as treatment successes, a dose response between the I-NO dose and decrease in PaO(2) after discontinuing I-NO was found. A reduction in I-NO to 1 ppm before discontinuation of the drug seems to minimize the decrease in PaO(2) seen. For infants failing treatment, discontinuation of I-NO could pose a life-threatening reduction in oxygenation should extracorporeal membrane oxygenation not be readily available or I-NO cannot be continued on transport.

Effect of routine intensive care interactions on metabolic rate.

The alterations in metabolic (oxygen consumption [VO2] and carbon dioxide production [VCO2]) and hemodynamic (heart rate and blood pressure) parameters caused by various common intensive care activities were examined in a group of 23 mechanically-ventilated critically-ill patients. The observed variations in metabolic rate can be classified into four categories as follows: (a) the lowest energy expenditure, which was associated with sleeping in the majority (83 percent) of instances; (b) resting, which was defined as a state where the patient was lying motionless with eyes open and responding to surrounding events, where VO2 and VCO2 averaged 9.1 +/- 7.5(SD) percent and 7.5 +/- 7.3 percent, respectively, above the lowest values; (c) a variety of routine daily care activities (eg, bathing, performing a physical examination) that although not particularly painful, caused arousal from the resting state. During these situations, VO2 and VCO2 averaged about 20 percent above lowest values; and (d) chest physical therapy, which was associated with metabolic increases of 35 percent above lowest values as well as increases in both heart rate and blood pressure. This study demonstrates that routine daily ICU activities can significantly alter metabolic rate, and thus, it is important to couple such measurements with astute observations of the patients' activity state. In addition, we have defined an activity state--resting--that can be used in the calculation of energy expenditure as well as for intrapatient and interpatient comparisons.

Do oxygen consumption and carbon dioxide production affect cardiac output after cardiopulmonary bypass?

This study examines the oxygen consumption (VO2) and carbon dioxide production (VCO2) occurring before, during, and after cardiopulmonary bypass (CPB) and whether they correlate with changes in cardiac output. Twenty-three patients undergoing open heart surgery were studied. Group 1 (N = 11) received fentanyl citrate, 50 micrograms/kg, intravenously during the induction of anesthesia. Group 2 (N = 12) received 100 micrograms/kg of fentanyl citrate intravenously. We measured VO2, VCO2, as well as hemodynamic and biochemical factors. Initial statistical analyses failed to show any differences in the VO2, VCO2, hemodynamic, or biochemical factors between groups 1 and 2. Therefore, the data from both groups were combined. In comparing the average (for all data) of the post-CPB with the pre-CPB periods in both groups for the metabolic factors, there were 9.0%, 11.5%, and 2.4% increases in the VO2, VCO2, and respiratory quotient, respectively. There was an 80% increase in total serum lactate levels seen in the post-CPB periods when compared with the pre-CPB periods. Serum triglyceride and free fatty acid levels measured in the post-CPB period decreased 39% and 25%, respectively, when compared with the pre-CPB periods. Although there were no changes in the cardiac outputs following CPB, the post-CPB periods showed a 37% increase in central venous pressure when compared with the pre-CPB periods. These data suggest that although there are significant metabolic and biochemical sequelae to CPB, the modest increases in post-CPB VO2, and VCO2 did not affect cardiac output following cardiovascular surgery. Increasing doses of narcotic do not have an effect on those relationships.

Abdominal aortic cross-clamping. Metabolic and hemodynamic consequences.

We address the question of whether an oxygen debt develops during a period of abdominal aortic cross-clamping that may explain observed hemodynamic changes. Group 1 received morphine sulfate (1 mg/kg) during induction of anesthesia. Group 2 received same dose of morphine sulfate. Group 3 received 4 mg/kg of morphine sulfate. We measured the oxygen consumption (VO2) and the carbon dioxide production levels (VCO2), as well as hemodynamic and biochemical parameters. In groups 1 and 3, VO2 and VCO2 decreased 10% to 13% following abdominal aortic cross-clamping compared with values measured before cross-clamping. In group 2, VO2 and VCO2 decreased 3% and 7%, respectively. On unclamping, the greatest increase in VO2 was observed in group 3 (26%), while in groups 1 and 2, VO2 rose 18% and 5%, respectively. In all three groups, metabolic changes were not paralleled by hemodynamic or temperature changes. Results indicate that oxygen debt developed during abdominal aortic cross-clamping, but this has no effect on hemodynamic changes seen after unclamping. Higher dosage of narcotic administered during anesthetic induction did not temper increase in metabolic rate observed after unclamping.

Combination hydrocodone and ibuprofen versus combination codeine and acetaminophen for the treatment of chronic pain.

OBJECTIVE: The objective of this study was to compare the effectiveness of combination hydrocodone 7.5 mg and ibuprofen 200 mg with that of combination codeine 30 mg and acetaminophen 300 mg for the treatment of chronic pain. BACKGROUND: Hydrocodone 7.5 mg with ibuprofen 200 mg is the only approved fixed-dose combination analgesic containing an opioid and ibuprofen. METHODS: In this randomized, parallel-group, double-blind, repeated-dose, active-comparator, 4-week, multicenter study, 469 patients were randomly assigned to receive a 1-tablet (n = 156) or 2-tablet (n = 153) dose of combination hydrocodone 7.5 mg and ibuprofen 200 mg (HI1 and HI2, respectively) or a 2-tablet dose of combination codeine 30 mg and acetaminophen 300 mg (CA, n = 160), the active comparator, every 6 to 8 hours as needed for pain. Efficacy was measured through pain relief scores, number of daily doses of study medication, number of daily doses of supplemental analgesics, number of patients who discontinued therapy due to an unsatisfactory analgesic response, and global assessment scores. RESULTS: Of the 469 patients, 255 (54.4%) were female and 214 (45.6%) were male. The mean age was 51.1 years. Types of chronic pain included back (214; 45.6%), arthritic (145; 30.9%), other musculoskeletal (65; 13.9%), cancer (6; 1.3%), diabetic neuropathic (3; 0.6%), postherpetic neuralgic (5; 1.1%), other neurologic (21; 4.5%), and other unclassified chronic pain (10; 2.1%). During the 48 hours prior to the study, 351 (74.8%) patients had been treated with opioid or opioid-nonopioid combination analgesics. The overall mean daily pain relief score was significantly greater in the HI2 group (2.25+/-0.89) than in the HI1 group (1.98+/-0.87) (P = 0.003) or the CA group (1.85+/-0.96) (P < 0.001). The overall mean number of daily doses of study medication was significantly less in the HI2 group (2.94+/-0.99) than in the HI1 group (3.23+/-0.76) (P = 0.036) or the CA group (3.26+/-0.75) (P = 0.014). The overall mean number of daily doses of supplemental analgesics was significantly less in the HI2 group (0.24+/-0.49) than in the HI1 group (0.34+/-0.58) (P = 0.021) or CA group (0.49+/-0.85) (P = 0.010). The number of patients who discontinued treatment due to an unsatisfactory analgesic response was significantly less in the HI2 group (2; 1.3%) than in the CA group (12; 7.5%) (P = 0.008). HI2 was more effective than HI1 and CA as measured by pain relief scores for week 1 (P < 0.001 vs HI1 and CA), week 2 (P < 0.001 vs HI1 and CA), and week 3 (P = 0.008 vs HI1 and P < 0.001 vs CA); daily doses of study medication for week 1 (P = 0.019 vs HI1 and P = 0.011 vs CA); daily doses of supplemental analgesics for week 1 (P = 0.010 vs HI1 and CA); and global assessment scores for week 1 (P = 0.018 vs HI1 and P < 0.001 vs CA), week 2 (P = 0.005 vs HI1 and P < 0.001 vs CA), and week 4 (P = 0.013 vs HI1 and P = 0.023 vs CA). There were no significant differences between HI1 and CA in any efficacy variable. There were no significant differences in the number of patients experiencing adverse events in the HI2 (127; 83%), HI1 (124; 79.5%), and CA (129; 80.6%) groups. However, the mean number of patients who discontinued treatment due to adverse events was significantly greater in the HI2 group (40; 26.1%) than in the HI1 group (23; 14.7%) (P = 0.013). CONCLUSIONS: The results of this study suggest that 2-tablet doses of combination hydrocodone 7.5 mg and ibuprofen 200 mg may be more effective than either 1-tablet doses of this combination or 2-tablet doses of combination codeine 30 mg and acetaminophen 300 mg. Moreover, 1-tablet doses of combination hydrocodone 7.5 mg and ibuprofen 200 mg may be as effective as 2-tablet doses of combination codeine 30 mg and acetaminophen 300 mg.

Dose-response effect of combination hydrocodone with ibuprofen in patients with moderate to severe postoperative pain.

OBJECTIVE: The objective of this study was to demonstrate a dose-response effect with 1- and 2-tablet doses of combination hydrocodone 7.5 mg with ibuprofen 200 mg and placebo in patients with moderate to severe postoperative abdominal or gynecologic pain. BACKGROUND: Hydrocodone 7.5 mg with ibuprofen 200 mg is the only approved fixed-dose combination analgesic containing an opioid and ibuprofen. Previous studies with this combination have demonstrated that the components have an additive analgesic effect as well as efficacy compared with other fixed-dose combination analgesics. METHODS: This randomized, parallel-group, double-blind, single-dose, placebo-controlled study compared 1 tablet of hydrocodone 7.5 mg with ibuprofen 200 mg (n = 60), 2 tablets of hydrocodone 7.5 mg with ibuprofen 200 mg (n = 60), and placebo (n = 60) in patients with moderate or severe pain after abdominal or gynecologic surgery. Analgesia was evaluated over 8 hours. RESULTS: Mean pain relief (PR) scores were significantly greater for the 2-tablet dose than for the 1-tablet dose at 80 (P = 0.027) and 100 (P = 0.017) minutes and at 2 (P = 0.013), 2.5 (P = 0.012), 3 (P = 0.006), 4 (P = 0.029), 5 (P = 0.002), 6 (P = 0.032), 7 (P = 0.036), and 8 (P = 0.01) hours. Mean pain intensity difference scores were significantly greater for the 2-tablet dose than for the 1-tablet dose at 80 (P = 0.013) and 100 (P = 0.007) minutes and at 2 (P = 0.003), 2.5 (P = 0.002), 3 (P = 0.002), 4 (P = 0.009), 5 (P < 0.001), 6 (P = 0.004), 7 (P = 0.009), and 8 (P = 0.001) hours. Mean total PR scores were significantly greater for the 2-tablet dose than for the 1-tablet dose for all measured time intervals (0 to 3 hours, P = 0.01; 0 to 4 hours, P = 0.006; 0 to 6 hours, P = 0.003; 0 to 8 hours, P = 0.003). Mean sum of pain intensity differences was significantly greater for the 2-tablet dose than for the 1-tablet dose for all measured time intervals (0 to 3 hours, P = 0.004; 0 to 4 hours, P < 0.001; 0 to 6 hours, P < 0.001; 0 to 8 hours, P < 0.001). Mean peak PR score and median time-to-remedication were significantly greater for the 2-tablet dose than for the 1-tablet dose (P < 0.029 and P = 0.017, respectively). Both doses were superior to placebo. There were no significant differences in the number of patients experiencing adverse events between the 2-tablet dose (n = 6 [10.0%]), the 1-tablet dose (n = 4 [6.7%]), and placebo (n = 1 11.7%]). Adverse events were not serious, and none of the patients discontinued therapy because of side effects. CONCLUSIONS: This study demonstrated that a 2-tablet dose of hydrocodone with ibuprofen provided significantly more analgesia than a 1-tablet dose (a positive dose-response effect) and that both doses were superior to placebo.

Combination hydrocodone and ibuprofen versus combination oxycodone and acetaminophen in the treatment of postoperative obstetric or gynecologic pain.

OBJECTIVE: The objective of this study was to compare the effectiveness of combination hydrocodone and ibuprofen with that of combination oxycodone and acetaminophen in the treatment of moderate to severe postoperative obstetric or gynecologic pain. BACKGROUND: Hydrocodone 7.5 mg with ibuprofen 200 mg is the only approved fixed-dose combination analgesic containing an opioid and ibuprofen. METHODS: This randomized, double-blind, parallel-group, single-dose, active-comparator, placebo-controlled study compared the effects of a 2-tablet dose of hydrocodone 7.5 mg and ibuprofen 200 mg with those of a 2-tablet dose of oxycodone 5 mg and acetaminophen 325 mg and placebo. Analgesia was assessed over 8 hours. RESULTS: Mean pain relief (PR) scores were similar for the hydrocodone with ibuprofen and oxycodone with acetaminophen groups (n = 61 and 59, respectively) at 0.5, 1, 1.5, 2, 2.5, 3, 4, and 7 hours and significantly greater for the hydrocodone with ibuprofen group at 5, 6, and 8 hours (P < or = 0.05). Mean pain intensity difference (PID) scores were similar for hydrocodone with ibuprofen and oxycodone with acetaminophen at 0.5, 1, 1.5, 2, 2.5, 3, and 4 hours and significantly greater for hydrocodone with ibuprofen at 5, 6, 7, and 8 hours (P < or = 0.05). Total PR scores were similar for hydrocodone with ibuprofen and oxycodone with acetaminophen for the 0- to 3- and 0- to 4-hour intervals and significantly greater for hydrocodone with ibuprofen for the 0- to 6- and 0- to 8-hour intervals (P < 0.05). The sum of the PID scores was similar for hydrocodone with ibuprofen and oxycodone with acetaminophen for the 0- to 3-, 0- to 4-, 0- to 6-, and 0- to 8-hour intervals. The median estimated time to onset of analgesia, mean peak PR score, median time to remedication, and mean global assessment score were similar for hydrocodone with ibuprofen and oxycodone with acetaminophen. Assay sensitivity was demonstrated by the presence of statistically significant differences between both active treatments and placebo (n = 60). The number of patients experiencing adverse events was similar for each of the 3 groups (11 [18.0%], hydrocodone with ibuprofen; 7 [11.9%], oxycodone with acetaminophen; and 6 [10.0%], placebo). CONCLUSIONS: In this study, a 2-tablet dose of combination hydrocodone 7.5 mg and ibuprofen 200 mg was as effective as a 2-tablet dose of combination oxycodone 5 mg and acetaminophen 325 mg in the treatment of moderate to severe postoperative obstetric or gynecologic pain. Both treatments were superior to placebo. The results of this study suggest that the combination of hydrocodone 7.5 mg and ibuprofen 200 mg may offer prescribers an additional option in combination pain therapy.

Energy measurements and requirements of critically ill patients.

The energy expenditure of the critically ill patient is influenced by many factors, thus making it difficult to predict. Measurement of energy expenditure in mechanically ventilated patients receiving elevated oxygen concentrations requires a good understanding of the measurement technique and its limitations, whether it be the gas exchange or Fick method. More investigation is needed to better understand the determinants of energy expenditure, as well as the total energy requirements of the critically ill patient.

General versus epidural anesthesia for femoral-popliteal bypass surgery.

This study examines whether epidural anesthesia is more effective than general anesthesia using an inhalation agent in controlling cardiovascular responses during femoral-popliteal bypass surgery. Nineteen patients were randomized into two groups: general anesthesia (n = 10) and epidural anesthesia (n = 9). The patients who underwent general anesthesia received sodium pentothal and succinylcholine for induction of anesthesia and 60% N2O, 40% O2, and 1% to 1.5% isoflurane for maintenance. Fifteen minutes before extubation, the patients received morphine sulfate 0.05 mg/kg intravenously (IV). The group that underwent epidural anesthesia received anesthesia to T-10 (through a catheter placed in the L4-5 interspace using 3% 2-chloroprocaine). Thirty minutes after the last dose, 0.05 mg/kg IV was administered. Hemodynamic variables were recorded at selected intervals during the operation and for 60 minutes in the recovery room. In the general anesthesia group, mean arterial pressure (MAP) and rate pressure product (RPP) significantly decreased (p less than 0.05) during the operation as compared with preoperative values. Following intubation and skin incision, 5 minutes after extubation, and after 60 minutes in the recovery room, MAP, heart rate (HR), and RPP were significantly greater (p less than 0.05) as compared with intraoperative periods. In the epidural anesthesia group, there were clinically important decreases in MAP and RPP after reaching T-10 and skin incision. The general anesthesia patients showed higher MAP, HR, and RPP 5 minutes after extubation and after 60 minutes in the recovery room. Epidural anesthesia patients showed stable hemodynamic patterns throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Is sufentanil removed by blood conservation devices?

To conserve blood during open heart surgery, cell savers and hemoconcentrators are used. Cell savers retrieve and filter shed blood from the operative field and then wash and separate reconcentrated erythrocytes from a supernatant by centrifugation. Hemoconcentrators are extracorporeal devices that extract an ultrafiltrate from the circulating perfusate during cardiopulmonary bypass. Both cell saver supernatant and hemoconcentrator ultrafiltrate are discarded. Twenty patients were anesthetized with a single dose of sufentanil, 30 microg/kg, and the cell saver supernatant and hemoconcentrator ultrafiltrate were analyzed for sufentanil. The supernatant contained only 0.1% of the total administered dose. Hemoconcentrators from two different manufacturers were tested, and 0.1% of the administered sufentanil was detected in one ultrafiltrate and none was found in the other. Thirty minutes after induction of anesthesia, the plasma sufentanil concentration was 8.5 ng/mL (1.3% of the given dose); 1 hour later, it was 4.9 ng/mL (0.8%). During cardiopulmonary bypass, the plasma level decreased to 2.5 ng/mL (0.6%); after bypass, it fell to 1.5 ng/mL (0.3%). It is concluded that intravenous (IV) sufentanil rapidly leaves the plasma compartment, and little remains available to be extracted by the devices used to process and conserve blood.

Evaluation of a non-invasive method for the measurement of metabolic rate in humans.

Measurements of oxygen consumption (VO2) and carbon dioxide production (VCO2) can be used to calculate energy expenditure. Such data are useful in the nutritional management of a variety of pathological conditions. This study is an evaluation in vitro and in vivo of the mating of a canopy and a Beckman metabolic measurement cart 1 (MMC). The canopy allows for the collection of expired gases without facial attachments. Studies in vitro demonstrated the necessity of calibrating the CO2 analyser at the concentrations used in such a system (0.50-0.80% CO2). Measurements of VO2 were within + 12% to -8% of predicted values, and when calibrated at 0.50% and 0.75% CO2, measurements of VCO2 were within + 2% and -7% of predicted values. The studies in vivo revealed that VO2 and VCO2 were within +/- 11% of the values obtained by using a canopy-spirometer-computer system. The MMC plus canopy may provide an alternative method for the clinical measurement of VO2 and VCO2, especially in subjects unable to tolerate a tight-fitting mask for prolonged periods.

Safety and potency of ANQ 9040 in male volunteers.

BACKGROUND: ANQ 9040 is an experimental nondepolarizing neuromuscular relaxant. Initial investigations in animals had indicated a rapid onset of action comparable to that of succinylcholine. The purpose of this study was to assess the safety and potency of ANQ 9040 in humans. METHODS: ANQ 9040 was assessed in 41 male volunteers. Anesthesia was induced with propofol and maintained with a propofol infusion and 60% N2O/40% O2. Neuromuscular function was measured by mechanomyography using train-of-four stimulation of the ulnar nerve every 12 s. After an initial pilot study, 23 volunteers received a single dose of ANQ 9040 of between 0.5 and 1.1 mg/kg to determine the dose-response relationship. The final 10 volunteers were given twice the estimated ED95 of ANQ 9040 as a single bolus dose. RESULTS: The estimated ED50 and ED95 of ANQ 9040 were 0.6 and 1.3 mg/kg, respectively. Apart from an increase in heart rate, no important adverse effects were noted after ANQ 9040 administration in the dose range 0.5-1.1 mg/kg. In the volunteers who received 2.6 mg/kg ANQ 9040, a substantial increase in plasma histamine was observed. This was associated with a 12% decrease in mean arterial pressure and a 49% increase in heart rate. In this group, the mean onset time to neuromuscular block was 51.3 s. CONCLUSIONS: ANQ 9040 is a rapid-onset neuromuscular blocking agent. However, twice the ED95 dose is associated with significant histamine release and tachycardia. This finding suggests that this drug will not be useful in clinical practice.

Artifacts in measurement of resting energy expenditure.

Measurements of gas exchange have been demonstrated to be clinically useful in the care of critically ill and malnourished patients. Using principles of indirect calorimetry, resting energy expenditure (REE) can be calculated from gas exchange data and used as the basis for designing a nutritional support regimen as well as for following the patient's metabolic state. This study demonstrates that a relatively minor procedure, such as percutaneous muscle biopsy, can induce temporary but major increases in gas exchange and lead to an overestimation of REE. Four studies were performed on 3 healthy adult subjects admitted to the Surgical Metabolism Unit for nutritional study. A percutaneous muscle biopsy was performed with the subject inside a canopy with continuous recording of oxygen consumption (VO2) and carbon dioxide production (VCO2). After the muscle biopsy, VCO2 and VO2 increased 93 and 103% (at their peak value), respectively. The mean duration that these changes persisted at least 15% above control was 10.6 +/- 7.8 (SD) and 11.4 +/- 5.9 min of VCO2 and VO2, respectively. Thus, considerable artifacts in the estimation of REE can occur due to painful stimuli.

A systematic method for validation of gas exchange measurements.

The measurement of gas exchange is useful, but thus far, has not been practical during the mechanical ventilation of critically ill patients. To validate two new commercial instruments, (Siemens-Elema Servo Ventilator 900B, Beckman Metabolic Cart), the authors constructed a lung model into which they delivered CO2 and N2 at precise rates to simulate Co2 production (Vco2) and O2 consumption (Vos). The model consists of 13.5-1 gas jar with an attached one liter anesthesia bag. The lung model was ventilated at present tidal volumes and frequencies. The authors also compared the measured respiratory quotient (RQ) with the known RQ of burning methanol (RQ = 0.67) in the jar. When the model was ventilated with levels of tidal volume and gas exchange applicable to adults, both instruments measured V02 within 5 to 13% of predicted values. Varying the FI02 did not significantly affect this accuracy. At tidal volumes below 350 ml, the difference increased between predicted VCO2 and measured VCO2. The difference between measured vs. the actual RQ of methanol was 5 and 1.5% in the Siemens-Elema and Beckman Systems, respectively.

Rapid 1% increases of end-tidal desflurane concentration to greater than 5% transiently increase heart rate and blood pressure in humans.

BACKGROUND: Large (0.5-1.0 MAC), rapid increases of desflurane to concentrations greater than 5% can transiently increase heart rate, mean arterial blood pressure (MAP), sympathetic nerve activity, and plasma epinephrine concentration. We tested the hypothesis that small (1% = 0.14 MAC), rapid increases of desflurane concentration to greater than 5% do not increase heart rate, blood pressure, and plasma catecholamine concentrations. METHODS: Anesthesia was induced with intravenous propofol, 2 mg/kg, in 13 healthy male volunteers, 19-33 yr of age, and ventilation was controlled to maintain normocapnia. We gave 4% end-tidal desflurane in oxygen for 32 min and then imposed successive 1% increases in end-tidal desflurane concentration, each new concentration maintained for 4 min, to a final concentration of 12%. We measured heart rate, MAP and plasma catecholamine concentrations in the awake state, after 4 min at each 1% step, and at times of peak increase of MAP (> or = 10% change). RESULTS: Increases in heart rate and blood pressure of more than 10% occurred with 1% step-increases in only 1 volunteer at 5% desflurane but in 7-10 (MAP) and 8-12 (heart rate) of the 13 volunteers at higher desflurane concentrations. The 1% increases in desflurane concentration to greater than 5% also transiently increased plasma epinephrine concentrations but not vasopressin concentration or plasma renin activity in those volunteers in whom MAP increased. CONCLUSIONS: Small (1%) increases in desflurane concentration to and greater than 6% can transiently increase heart rate, mean arterial pressure, and plasma epinephrine concentration. These data and those from a previous study indicate that these increases occur with a lesser frequency and magnitude than those associated with a single, rapid step from 4% to 12% end-tidal desflurane.

Physiologic requirements during rewarming: suppression of the shivering response.

Intraoperative hypothermia has become a common occurrence. Postoperative rewarming often is accompanied by shivering and results in increased metabolic and circulatory demands. We examined the metabolic, hemodynamic, and biochemical variables in 2 groups of hypothermic (greater than 35.8 degrees C) patients requiring mechanical ventilation after a major operation. One was observed during routine medical management whereas the other group received 40 mg of metocurine iodide and then observed during routine medical management. All patients were allowed to rewarm passively. O2 consumption (VO2, ml/min, STPD), CO2 production (VCO2, ml/min, STPD) and respiratory quotient (RQ) measurements were made every 15 min using a Beckman Metabolic Measurement Cart. Esophageal temperature, arterial blood pressure, heart rate (HR), rate pressure product, CVP, arterial blood gases, serum lactate concentration, and duration of shivering also were recorded. Suppression of the shivering by metocurine increased rewarming time significantly and decreased VCO2, VO2, HR, rate pressure product, mean arterial pressure (MAP), and the O2 cost of rewarming. Thus, the elimination of shivering during postoperative rewarming is associated with a decrease in caloric, metabolic demands and myocardial work (as assessed by the rate pressure product) while rewarming time is prolonged. In the postoperative, hypothermic, critically ill patient, suppression of the shivering response in selected patients may be indicated.

Morphine and postoperative rewarming in critically ill patients.

Morphine sulfate (MSO4) has been demonstrated to attenuate the stress response. MSO4 might be useful in minimizing the stress associated with the perioperative period, particularly that due to awakening from anesthesia and rewarming. Two groups of critically ill patients who developed hypothermia (35.8 degrees C) during a surgical procedure were studied. The control group was observed during routine medical management. Group II received 1 or 4 mg/kg MSO4 followed by an infusion of 0.2 or 0.5 mg/kg/hr. During the postoperative rewarming period the control group patients demonstrated a major increase in metabolic demand and myocardial work. In group II patients the infusion of MSO4 resulted in a lower metabolic rate. This was associated with a significantly longer rewarming time and a significant reduction in shivering, heat loss, heart rate, mean arterial pressure, and rate-pressure product. Infusion of MSO4 in critically ill patients during the perioperative period suppressed metabolic demands and myocardial work while preserving cardiovascular function.

Response to tubular airway resistance in normal subjects and postoperative patients.

Critically ill patients must often breathe spontaneously through an endotracheal tube that acts as a fixed inspiratory and expiratory tubular airway resistor. Although this practice is common, its effect on the pattern of breathing is not known. The mean breathing patterns of seven normal, healthy male subjects and eight male patients who had undergone upper abdominal surgery 2-4 days previously were studied breathing through a mouthpiece fitted in random order with a 5, 6, 7, 8, or 15 mm diameter (17 mm long) resistor. These diameters were selected because they simulate the pressure-flow relationships of adult endotracheal tubes. With the 15 mm aperture, the patients had a greater breathing frequency (f) than did the normal subjects (21 +/- 5 [SD] vs. 14 +/- 4 breaths/min, P less than 0.01) as well as a smaller mean tidal volume (VT). In both groups, minute ventilation (VE) and f progressively decreased as resistance was increased by decreasing the aperture size from 15 to 16 mm. In the normal subjects but not the patients, VT also progressively decreased. When the diameter was decreased from 6 mm to 5 mm, there were increases in VT and decreases in f that were more marked in the normal subjects. In both groups, the changes in VE were accompanied by decreases in mean and peak inspiratory and expiratory flow rates. Throughout the study, oxygen consumption (VO2) and carbon dioxide production (VCO2) did not change. This, coupled with the decreases in VE resulted in decreases in the ventilatory equivalents to CO2 and O2 (VE/VCO2, VE/VO2).(ABSTRACT TRUNCATED AT 250 WORDS)