[The i-STAT analyzer. A new, hand-held device for the bedside determination of hematocrit, blood gases, and electrolytes]. / Der i-STAT Analyzer. Ein neues, tragbares Gerät zur Bedsidebestimmung des Hämatokrits, der Blutgase und Elektrolyte.

UNLABELLED: Exact and quick measurements of basic laboratory parameters are important in selected patients in the perioperative period. Depending on the capabilities of a hospital's central laboratory, the anaesthesiologist may only obtain such laboratory tests after unacceptable delays. This problem may be overcome by a new bedside measurement device that has become available from i-STAT Corporation, Princeton, USA. The hand-held, battery-driven analyser accepts blood specimens that are injected into a disposable cartridge (EG7+) and measures acidity, blood gas tensions, haematocrit, and electrolytes. The aim of this study was to determine the accuracy of such measurements by comparing them with measurements obtained by conventional laboratory test methods. METHODS: Heparinised arterial blood specimens were collected in duplicate from 49 surgical patients. Measurements of ionised calcium (Ca), sodium (Na), potassium (K), pH, pCO2, pO2, base excess (BE), haematocrit (Hct), and haemoglobin (Hb) obtained by the i-STAT analyser were compared with measurements from the calibrated analysers ABL 615 and EML 100 (Radiometer, Copenhagen). Because the i-STAT analyser calculates the Hb concentration from a conductometrically measured Hct, 19 blood specimens were centrifuged in order to compare test results with conventionally obtained Hct and Hb values. As the Hct test sensitivity with the i-STAT changes with diluted blood due to its low albumin concentration, Hct and Hb measurements during cardio-pulmonary bypass (CPB) must be corrected by activating an analyser-implemented correction algorithm (Hct/CPB and Hb/CPB). Correlation analysis was performed between conventional measurements and i-STAT values (Ca, Na, K, Hct, pCO2, pO2), between values that the i-STAT analyser derives (Hb, HCO3, BE) and conventionally obtained results, and between normal and CPB-corrected Hct and Hb values. Accuracy was judged according to the national quality standard, which requires test results to lie within the 95% confidence interval of conventional tests. RESULTS: Each blood specimen was analysed: erroneous results or technical failures did not occur. Measurement of one set of i-STAT values required 2.5 min. Correlation coefficients (r) between conventional and i-STAT results were: 0.85 for CA, 1.0 for K; 0.86 for Na; 0.99 for pH; 0.98 for pCO2; 0.99 for pO2; 0.93 for HCO3; 0.93 for BE; 0.46 for Hb values not corrected for CPB and 0.95 for CPB-corrected Hb; and 0.74 for Hct values not corrected for CPB and 0.98 for CPB-corrected Hct. The correlation coefficient for Hct between centrifuged and CPB-uncorrected i-STAT values was 0.81 and that for CPB-corrected values was 0.98. National accuracy requirements were not met for tests of: Ca (by 0.02 mmol/l); pH (by 0.01); pO2 including hyperoxic values (by 26.7 mmHg, but were met for pO2 values < 200 mmHg); Hb (by 1.6 g/dl); Hb/CPB (by 0.8 g/dl); and Hct (by 6.5%, but were met for Hct/CPB values). All other tests fulfilled the required standards. CONCLUSION: This analyser is easy to use, reliable, and portable, and therefore suitable for the operating room, for analyses during emergencies, on peripheral wards, for preclinical screening, or at times when availability of lab tests is time-consuming or limited. The test accuracy for electrolytes, blood gases, and Hb is high enough to justify routine use of the i-STAT analyser in clinical practice. That the nationally required quality standards for Ca, pH, and Hb were not met is not of importance because the measured deviation was too small to have clinical relevance. When analysing diluted blood with a low Hct and low oncotic pressure, it is important to activate the analyser's correction algorithm "CPB", because the obtained results will then comply with the required accuracy.

[Intravenous sedation of spontaneously breathing infants and small children before magnetic resonance tomography. A comparison of propofol and methohexital]. / Intravenöse sedierung von spontanatmenden Säuglingen und Kleinkindern während der Magnetresonanztomographie. Ein Vergleich zwischen Propofol und Methohexital.

UNLABELLED: The purpose of the present study was to compare two sedation regimens with either propofol (P) or methohexital (M) for elective magnetic resonance imaging (MRI) in children with respect to safety, side effects, recovery, and discharge time. METHODS: After Institutional Review Board approval, 120 unpremedicated children with a mean age of 26.5 +/- 21.4 months (M) and 28.1 +/- 19.9 months (P) were randomly assigned to receive a hypnotic induction dose of either M or P. Supplemental bolus injections of M or P were administered to maintain adequate sedation. The following parameters were measured: heart rate, oxygen saturation by pulse oximetry (SpO2), respiratory rate, end-tidal CO2 (PetCO2), side effects, and recovery and discharge times. RESULTS: Spontaneous respiration was maintained in all patients, and ventilatory support was only necessary for 2 min in 1 M patient immediately after the induction dose. The mean loading and total doses for M were 2.3 +/- 0.7 and 6.1 +/- 3.3 mg/kg respectively, and for P 2.3 +/- 0.9 and 5.8 +/- 2.7 mg/kg. Following induction SpO2 < 90% occurred in 0.49% with M and in 0.64% with P (n.s.). Apnoe > 20s was observed in 2 children each after M and P (n.s.). The frequency of hypoventilation (PetCO2 > 48 mmHg) was 0.36% in the M group and 0.71% in the P group (n.s.). MRI sequences had to be repeated in 5% of the children in each group because of spontaneous movements. The heart rate fell significantly during MRI in both groups, while P children had lower frequencies than M children (P < 0.01). Recovery and discharge times were significantly shorter in the P group, at 0.8 min (0.08-4.8) and 2.2 min (0.2-15.0), compared to 1.5 min (0.3-28.5) and 3.5 min (0.6-40.0) in patients receiving P (P < 0.01). No patient required admission to the postanaesthesia care unit and all were free from nausea and vomiting. DISCUSSION: Intravenous sedation with M or P using the reported technique is a safe regimen for children undergoing elective MRI. The fast recovery and discharge times seem to offer advantages over general anaesthesia with endotracheal intubation. The faster recovery and discharge of only a few minutes after P compared with M is without clinical relevance.

[Addition of fentanyl to bupivacaine--peridural analgesia in cesarean section]. / Zusatz von Fentanyl zur Bupivacain--Periduralanalgesie bei Sectio Caesarea.

UNLABELLED: Epidural anaesthesia for elective caesarean section can have advantages over general anaesthesia. The anaesthesiologist can avoid endotracheal intubation as well as fetal depression following placental transfer of systemic anaesthetics. However, despite reaching an effective blockade preoperatively, intraoperative discomfort and pain may occur during epidural anaesthesia with local anaesthetics alone, necessitating supplemental systemic analgesics or even conversion to general anaesthesia [21]. Addition of epidural fentanyl has been shown to improve onset and quality of perioperative analgesia without evident side effects for mother or newborn [24]. Nevertheless, administration of epidural opioids before cord clamping is still hotly debated, some fearing maternal and or neonatal depression [6, 26]. The aim of the present study was to investigate the quality of analgesia, associated side effects and the resulting maternal and neonatal plasma opiate concentrations after a single preoperative addition of 0.1 mg fentanyl to epidural bupivacaine analgesia in comparison to epidural bupivacaine analgesia alone. METHODS: Following governmental and ethics committee approval, 43 elective consenting patients for caesarean section were randomized to receive double-blind injections of either 8 ml 0.5% bupivacaine(+)0.1 mg fentanyl (B+F group, n = 22) or 8 ml 0.5% bupivacaine +2 ml saline (Bup group, n = 21) into an epidural catheter. In both groups additional injections of bupivacaine were given to achieve sensory blockade up to T4. Systolic blood pressure, heart and respiratory rates were measured regularly. Quality of intraoperative pain relief was assessed at delivery, uterine eventration, and during uterine and abdominal closure using a visual analogue scale (VAS). The duration of postoperative analgesia was compared between groups, as well as the incidence of nausea, itching or sedation. Similarly, Apgar scores and umbilical arterial and venous blood gas analyses were compared. Fentanyl concentrations were determined in maternal venous blood sampled before and 20 and 40 min after epidural injection and at birth, and in umbilical venous and arterial blood sampled after delivery. Radioimmunoassay analysis was performed from plasma specimens centrifuged and frozen at -20 degrees C [19]. The statistical level of significance was defined as P < 0.05. RESULTS: Groups were comparable regarding age, weight and time of gestation. Total bupivacaine doses and injection to delivery times were similar in both groups. Figure 1 shows that there were 40% more pain-free (VAS = 0) patients in the B+F group during uterine eventration and wound closure (P < 0.05). Mean postoperative duration of analgesia was significantly longer in the B+F group (382 vs 236 min). The rate of nausea and mild itching was significantly higher in the B+F group. Respiratory depression was never detected in patients or newborns. Small group differences in blood pressure or respiratory rate were inconstant and clinically irrelevant, as were differences in umbilical venous pCO2. One hundred and twenty-five blood samples were analysed for fentanyl concentrations. The mean fentanyl concentration before epidural injection was not zero, but 0.25 ng/mg (range 0.02-0.32). Maternal concentrations at 20 and 40 min after injection were 0.55 ng/ml (0.12-1.14) and 0.52 ng/ ml (0.26-1.04) (Fig. 3). At delivery, mean maternal fentanyl concentration was 0.58 ng/ml (0.14-1.18); mean umbilical arterial and venous concentrations were 0.51 ng/ml (0.04-1.8) and 0.41 ng/ml (0.18- 1.2), respectively. Rare results of fentanyl concentrations > 1.0 ng/ml correlated neither with sedation, maternal respiratory rate and side effects, nor with Apgar scores and umbilical blood gas values. No Apgar score at 5 min was below 9, and no umbilical pH was below 7.20. (ABSTRACT TRUNCATED)

[Effect of halothane, enflurane and isoflurane on the pharmacodynamics of mivacurium in children]. / Einfluss von Halothan, Enfluran und Isofluran auf die Pharmakodynamik von Mivacurium bei Kindern.

INTRODUCTION AND OBJECTIVE: Mivacurium is a new non-depolarising muscle relaxant with a relatively rapid onset and short duration of action. In children, intravenous injection of 0.2 mg/kg produces satisfactory relaxation. Because inhalational anaesthetics have been found to enhance the potency of muscle relaxants we determined if onset or recovery times following mivacurium are influenced by inhalation of halothane (HAL), enflurane (ENF) or isoflurane (ISO). METHODS: After intramuscular induction, 36 surgical children (2-6 years, ASA I) were randomly assigned to inhale either HAL (n = 12); ENF (n = 12) or ISO (n = 12). The train-of four (TOF) response was determined electromyographically (Relaxograph, Datex) at 20-second time intervals. Following ten minutes of inhalation of either HAL, ENF or ISO (0,8; 1,2; 1,0 vol% respectively) in N2 O/O2 (2:1), 0.2 mg/kg of mivacurium was injected intravenously. Patients were intubated at maximal T1-suppression and the intubating conditions were judged according to a graded score. Upon recovery of T1 = 25%, six patients in each group were antagonised with 30 micrograms/kg of neostigmine and 15 micrograms/kg of atropine; the recovery indices were compared with those from non-antagonised patients. Differences between groups were tested with multifactorial analysis of variance (p < 0.05). RESULTS: Intubating conditions were graded as "excellent" or "good" in all patients but one who showed moderate breath holding following the tube passage. Onset times of mivacurium were not different between patients receiving HAL: 2.4 min +/- 0.52 (+/ SD); ENF: 2.4 min +/- 0.55 or ISO: 2.6 min +/- 0.68. Time to T1 = 25% was 7.6 min +/- 2.91 (HAL); 7.9 min +/- 1.55 (ENF) and 8.6 min +/- 2.30 (ISO). Recovery indices were not significantly different between groups. Total duration of action in non-antagonised patients was 13.0 min +/- 3.32 (HAL); 14.3 min +/- 4.01 (ENF) and 19.6 min +/- 5.17 (ISO), whereas antagonised duration of action was 13.4 min +/- 5.11 (HAL); 13.3 min +/- 1.97 (ENF) and 15.6 min +/- 4.25 (ISO). The shorter total duration of action in patients receiving neostigmine (average 0.5-2 minutes) was statistically insignificant. DISCUSSION AND CONCLUSION: Following injection of 0.2 mg/kg of mivacurium, no clinically relevant differences in onset or recovery times were found between children receiving halothane, enflurane or isoflurane. No differences in heart rate or blood pressure were found between groups. Compared to previous investigations with mivacurium, we noted a 30-60% longer mean onset time and a 30% shorter mean spontaneous recovery time. This may be explained by the lower mean age of our patients, which correlates with a relatively higher volume of distribution, resulting in lower plasma concentrations if the dose is calculated per kilogramme body weight. The reduction of the mean recovery time by 2 minutes following neostigmine injection seems to be clinically irrelevant. Similar to adult, a twofold ED95 produces satisfactory surgical muscle relaxation in children receiving mivacurium. Thus, its onset time is comparable to that of vecuronium or atracurium. The shorter duration of action offering a tighter control over relaxation may be of clinical advantage in this age group.

[Repeated addition of fentanyl to bupivacaine peridural analgesia in labor. Clinical action and fentanyl plasma level]. / Wiederholter Zusatz von Fentanyl zur peripartalen Bupivacain-Periduralanalgesie. Klinische Wirkung und Fentanyl-Plasmaspiegel.

A combination of epidural opioids with local anaesthetics has been used to improve pain relief during labor and to reduce side effects, such as muscle weakness, usually seen when local anaesthetics are used alone. The addition of epidural fentanyl (F) produces highly effective analgesia, the only side effect being mild itching. Initial trials investigated the improvement in analgesia after a single administration of F during first- but not during second-stage labor. Even though pain perception during second-stage labor under epidural analgesia with local anaesthetics can be severe, the addition of opioids was avoided for fear of neonatal or maternal depression. A recent report found maternal and umbilical plasma concentrations following injection of 100 micrograms F to be safe and the investigators speculated that repeated addition of epidural/F to injection of local anaesthetic may prove beneficial for the parturient without exposing the mother or fetus to risk. We therefore studied maternal analgesia, maternal and umbilical plasma levels and associated side effects following repeated addition of 100 micrograms F to bupivacaine epidural analgesia during labor. METHODS. Following institutional and governmental approval 53 parturients were randomly assigned to receive either 8 ml bupivacaine 0.25% + 0.1 mg fentanyl (B + F group; n = 28) or 8 ml bupivacaine 0.25% + 2 ml saline (BUP group; n = 25) in an epidural catheter at L2/3. The same dose was reinjected upon the patients' request regardless of the degree of cervical dilatation. Blood pressure, heart rate, respiratory rate and the incidence of side effects were recorded before and following each epidural injection. Pain relief was determined at each injection and following cord clamping using the visual analogue pain scale (VAS; 0-100 mm). Maternal venous blood samples were collected to measure plasma F concentrations before and 20 and 40 min after each injection and at birth when umbilical venous and arterial blood was obtained. After centrifugation the samples were maintained at -20 degrees C and then analyzed by radioimmunoassay. At delivery, Apgar scores and umbilical venous and arterial blood gas values were determined. RESULTS. Both groups were comparable for age, weight, height, gestational age and parity. A total of 48 epidural injections were evaluated in the B + F group, 43 in the BUP group. No statistically significant group difference was found between the frequency of injections per delivery (B + F: 2.2; BUP: 1.8); regarding the time between the initial and the first top-up dose (B + F: 144 min; BUP: 140 min) or regarding the interval between the last injection and birth (B + F: 94 min; BUP; 90 min). However, the quality of pain relief during labor and particularly at birth was significantly improved by F (mean VAS in B + F group: 6 mm; mean VAS in BUP group: 42 mm). Mild itching was observed in 43% of patients receiving F, moderate shivering in 13% versus 40% in patients not receiving F. At control mean maternal F plasma levels were not zero but 0.25 ng/ml. After the initial injection and following the first and second top-up dose mean maximum maternal F plasma concentrations were 0.54 ng/ml (+/-0.32; +/-SD), 0.88 ng/ml (+/-0.62) and 1.06 ng/ml (+/-0.4) (range 0.18-2.76 ng/ml), respectively. The increase in maternal F concentrations with increasing injection frequency was statistically significant (P < 0.02). Mean umbilical venous and arterial F concentrations at birth were 0.72 ng/ml (+/-1.16) and 0.62 ng/ml (+/-0.52). No significant group differences were found regarding Apgar scores or umbilical blood gas analyses. In one newborn, radioimmunoassay resulted in unexplainably high umbilical F concentrations without any clinical signs of sedation, depressed vigilance and without any sequellae. DISCUSSION. Repeated addition of 100 micrograms F to epidural anaesthesia with bupivacaine significantly improves analgesia and provides pain relief not only during the fir

[Uptaken distribution and metabolism of sevoflurane]. / Aufnahme, Verteilung und Metabolismus von Sevofluran.

The inhalational anaesthetic fluor-methyl-trifluor-1-(trifluoromethyl)-ethylether sevoflurane has been known for more than 20 years and is structurally related to the currently available volatile anaesthetics. This anaesthetic is characterized by a low blood/gas partition coefficient of 0.69 and high fat solubility, leading to a sharp rise in alveolar concentration and quick anaesthesia induction. As opposed to desflurane, sevoflurane does not boil at ambient temperature, thus making a special vaporizer unnecessary. The alveolar uptake of sevoflurane is 20% and 66% faster than that of isoflurane and halothane respectively. Elimination of sevoflurane from the blood is twice as quick as that of halothane; the younger the patient, the earlier awakening from anaesthesia occurs. When administered in oxygen the minimal anaesthetic concentration (MAC) of sevoflurane in adults is 1.71 vol%; when administered in 60% nitric oxide, the MAC decreases to 0.66 vol%. The variations of published MAC determinations seem to results from geographical or population-specific potency differences of sevoflurane. In children MAC varies between 2.03 and 2.49 vol%. Biodegredation of sevoflurane occurs immediately following inhalation, leading to separation of ionized and of organically bound fluoride. As opposed to methoxyflurane, which may be nephrotoxic due to its microsomal metabolism in kidney tissue, sevoflurane does not seem to cause clinical inhibition of renal function even at plasma fluoride levels above 50 mumol/l, a concentration thought to be associated with renal tubular impairment. A possible reason for this observation is lower metabolism of sevoflurane within renal tissues. Due to its quick onset and fast elimination, sevoflurane is an interesting new volatile anaesthetic offering various clinical advantages.

Droperidol causes a dose-dependent prolongation of the QT interval.

To further investigate possible prolongation of the frequency-corrected QT interval (QTc interval) after administration of droperidol (DRO), we studied 40 surgical patients who were randomly assigned to one of three groups, receiving an intravenous (IV) injection of either 0.1 mg/kg (Group 1, n = 10), 0.175 mg/kg (Group 2, n = 10), or 0.25 mg/kg (Group 3, n = 20) of DRO at induction of anesthesia. The QTc interval, heart rate, and arterial pressure were registered before and 1, 2, 3, 4, 5, 7.5, and 10 min after the respective dose injection. Significant prolongations of the median QTc interval were found in patients from all groups, ranging from 37 ms (8.0%) in Group 1, to 44 ms (10.6%) in Group 2, to 59 ms (14.9%) in Group 3, when compared with control. The heart rate showed a significant increase in all groups. Mean arterial pressure (MAP) was slightly but significantly decreased in Groups 1 and 3. Prolongation of the QTc interval is a predictable and dose-dependent side effect after injection of high-dose DRO.

Midazolam does not antagonize fentanyl-mediated analgesia in surgical patients.

STUDY OBJECTIVE: To determine whether midazolam possesses a clinically significant antianalgesic action in surgical patients. DESIGN: Randomized, controlled study. SETTING: Inpatient anesthesia at a university department of neurosurgery. PATIENTS: 2 groups of 10 patients each who were scheduled for supratentorial brain surgery, did not have elevated intracranial pressure, and were free from systemic disease. INTERVENTIONS: Patients underwent anesthesia induction with hexobarbital, succinylcholine, and pancuronium; anesthesia was maintained with injections of droperidol-fentanyl (Group 1) or with midazolam-fentanyl (Group 2) following a predetermined repetitive dosing schedule, such that fentanyl 0.1 mg was injected upon predominant increases in heart rate, whereas droperidol 2.5 mg or midazolam 2.5 mg was injected upon increases in blood pressure. MEASUREMENTS AND MAIN RESULTS: Duration of anesthesia and invasiveness of surgery were similar in both groups. The amount of fentanyl required was 0.55 +/- 0.18 mg/hr (mean +/- SD) in Group 1 and 0.53 +/- 0.17 mg/hr in Group 2. Injections of droperidol 7.5 +/- 3.4 mg/hr (Group 1) and midazolam 5.9 +/- 2.3 mg/hr (Group 2) were administered intraoperatively. This redosing regimen was associated with uninterrupted hemodynamic stability, indicating comparable and adequate anesthetic depth. Plasma concentrations of metabolites and hormones indicative of humoral stress activation did not differ between groups. CONCLUSION: Under these clinical conditions, the administration of midazolam, when compared with droperidol, was not associated with signs of any antagonistic or antianalgesic action toward fentanyl-mediated analgesia.

Gas exchange in dogs in the prone and supine positions.

To determine the cause of the difference in gas exchange between the prone and supine postures in dogs, gas exchange was assessed by the multiple inert gas elimination technique (MIGET) and distribution of pulmonary blood flow was determined using radioactively labeled microspheres in seven anesthetized paralyzed dogs. Each animal was studied in the prone and supine positions in random order while tidal volume and respiratory frequency were kept constant with mechanical ventilation. Mean arterial PO2 was significantly lower (P less than 0.01) in the supine [96 +/- 10 (SD) Torr] than in the prone (107 +/- 6 Torr) position, whereas arterial PCO2 was constant (38 Torr). The distribution of blood flow (Q) vs. ventilation-to-perfusion ratio obtained from MIGET was significantly wider (P less than 0.01) in the supine [ln SD(Q) = 0.75 +/- 0.26] than in the prone position [ln SD (Q) = 0.34 +/- 0.05]. Right-to-left pulmonary shunting was not significantly altered. The distribution of microspheres was more heterogeneous in the supine than in the prone position. The larger heterogeneity was due in part to dorsal-to-ventral gradients in Q in the supine position that were not present in the prone position (P less than 0.01). The decreased efficiency of oxygenation in the supine posture is caused by an increased ventilation-to-perfusion mismatch that accompanies an increase in the heterogeneity of Q distribution.

Direct and neurally mediated effects of halothane on pulmonary resistance in vivo.

It has been suggested that halothane inhibits contraction of airway smooth muscle in vivo mainly by reducing reflex activity in nerves innervating the muscle with only minimal direct effects on the muscle itself. To examine possible mechanisms of action of halothane at clinically relevant concentrations the authors studied the effect of halothane on increases in pulmonary resistance (RL) produced by either vagus nerve stimulation (VNS, which caused neurally mediated constriction) or the inhalation of nebulized acetylcholine (ACh, which directly stimulated the smooth muscle cell) in nine mongrel dogs. The frequency of bilateral VNS and the dose of nebulized ACh were adjusted to produce approximately equal increases in RL. Halothane reduced the response to both types of stimulation in a dose-dependent fashion. At halothane concentrations greater than or equal to 0.4 MAC, the VNS response was significantly less than the ACh response. When tetrodotoxin was given to block neural activity, the ACh response was unchanged, confirming that neural activation did not contribute significantly to smooth muscle contraction in response to ACh. The authors conclude that in addition to neurally mediated effects, halothane at clinically used concentrations has significant direct effects on airway smooth muscle stimulated by ACh. The relative importance of each factor in vivo should depend on the stimulus that causes contraction of airway smooth muscle.

Halothane decreases both tissue and airway resistances in excised canine lungs.

Studies of the anesthetic effects on the airway often use pulmonary resistance (RL) as an index of airway caliber. To determine the effects of the volatile anesthetic, halothane, on tissue and airway components of RL, we measured both components in excised canine lungs before and during halothane administration. Tissue resistance (Rti), airway resistance (Raw), and dynamic lung compliance (CL, dyn) were determined at constant tidal volume and at ventilatory frequencies ranging from 5 to 45 min-1 by an alveolar capsule technique. Halothane decreased RL at each breathing frequency by causing significant decreases in both Raw and Rti but did not change the relative contribution of Rti to RL at any frequency. Halothane increased CL,dyn at each breathing frequency, although there was little change in the static pressure-volume relationship. The administration of isoproterenol both airway and tissue components of RL; it may act by relaxing the contractile elements in the lung. Both components must be considered when the effects of volatile anesthetics on RL are interpreted.

Position and motion of the human diaphragm during anesthesia-paralysis.

Regional motion of the human diaphragm was determined by high-speed, three-dimensional x-ray computed tomography. Six healthy volunteers were studied first while awake and breathing spontaneously and again while anesthetized-paralyzed and their lungs ventilated mechanically. Tidal volume (VT) and respiratory frequency were similar during both conditions. Three subjects were studied while they were supine and three while they were prone. During spontaneous breathing, movement of dependent diaphragm regions was greater than that of nondependent regions in four of six subjects. In five of the six subjects, dorsal diaphragm movement exceeded ventral movement regardless of body position. The volume displaced by the diaphragm (delta Vdi) was similar to VT in supine subjects but tended to be less than VT in prone subjects. After induction of anesthesia-paralysis, the end-expiratory position of the diaphragm did not change consistently in supine subjects, whereas a consistent cephalad volume shift occurred in prone subjects. During anesthesia-paralysis and mechanical ventilation, delta Vdi was reduced to approximately 50% of VT in both body positions. In the supine position, the pattern of diaphragm motion during mechanical inflation was nearly uniform. By contrast, in the prone position, the motion was nonuniform, with most motion occurring in the dorsal (nondependent) regions. It is concluded that the dominant influence on diaphragm motion may be some anatomical difference between the crural and costal diaphragm regions rather than the abdominal hydrostatic pressure gradient.

Pulmonary resistance during halothane anesthesia is not determined only by airway caliber.

Studies of the effect of halothane on airway smooth muscle have used pulmonary resistance as an index of airway caliber. However, pulmonary resistance (RL) is the sum of airway resistance (Raw), which changes with airway caliber, and of tissue resistance (Rti), which depends on the pressure-volume hysteresis of the lung. To separate the effects of halothane on airway caliber from its possible effects on tissue pressure-volume hysteresis in the unstimulated lung and during bronchoconstriction, the authors measured both components of RL before and during vagus nerve stimulation in 12 dogs before and during halothane administration. Rti was always the major component of RL, constituting 77 +/- 14% (mean +/- SD) of RL before vagus nerve stimulation and 64 +/- 21% of RL during stimulation in the absence of halothane. Vagus nerve stimulation caused approximately equal increases in both Rti and Raw. Halothane attenuated the response of both Rti and Raw to vagus nerve stimulation in a dose-dependent fashion. At 1 MAC, the Rti response was 44 +/- 13% of its value before halothane administration and the Raw response was 32 +/- 12% of its value before halothane administration; these responses were not significantly different. The authors conclude that changes in RL during halothane administration are caused not only by changes in airway caliber, as previously assumed, but also reflect a significant effect of halothane on lung tissue pressure-volume hysteresis.

Volume quantification of chest wall motion in dogs.

We employed high-speed multisliced X-ray-computed tomography to determine the relative volume contributions of rib cage (delta Vrc) and diaphragmatic motion (delta Vdi) to tidal volume (VT) during spontaneous breathing in 6 anesthetized dogs lying supine. Mean values were 40 +/- 6% (SE) for delta Vrc and 62 +/- 8% of VT for delta Vdi. The difference between VT and changes in thoracic cavity volume was taken to represent a change in thoracic blood volume (2 +/- 3% of VT). To estimate how much of delta Vrc was caused by diaphragmatic contraction and how much of delta Vdi was caused by rib cage motion, delta Vrc and delta Vdi were determined during bilateral stimulation of the C5-C6 phrenic nerve roots in the apneic dog and again during spontaneous breathing after phrenicotomy. Thoracic cavity volume (Vth) measured during hypocapnic apnea was consistently larger than Vth at end expiration, suggesting that relaxation of expiratory muscles contributed significantly to both delta Vrc and delta Vdi during spontaneous inspiration. Phrenic nerve stimulation did not contribute to delta Vrc, suggesting that diaphragmatic contraction had no net expanding action on the rib cage above the zone of apposition. Spontaneous breathing after phrenicotomy resulted in small and inconsistent diaphragmatic displacement (8 +/- 4% of VT). We conclude that the diaphragm does not drive the rib cage to inflate the lungs and that rib cage motion does not significantly affect diaphragmatic position during spontaneous breathing in anesthetized dogs lying supine.

Actions of enflurane, isoflurane, vecuronium, atracurium, and pancuronium on pulmonary resistance in dogs.

The effects of enflurane, isoflurane, vecuronium, atracurium, and pancuronium on pulmonary resistance and heart rate were studied in 30 vagotomized dogs lying supine and anesthetized with chloralose-urethane. None of the five drugs affected pulmonary resistance when the airway was unstimulated. Enflurane and isoflurane significantly attenuated the increase in pulmonary resistance induced by electrical stimulation of the vagus nerves. This effect was dose-dependent and similar for both anesthetics at equivalent multiples of their minimum alveolar concentration. Atracurium significantly (P less than 0.05) enhanced the increase in pulmonary resistance induced by vagus nerve stimulation; vecuronium had no significant effect. Pancuronium, up to a cumulative dose of 0.14 mg/kg, also significantly (P less than 0.05) enhanced the increase in pulmonary resistance induced by vagus nerve stimulation; but this effect was reversed by further increasing the dose. Pancuronium also attenuated the cardiodecelerator response to vagus nerve stimulation in a dose-dependent fashion. The underlying mechanisms for the attenuation of responses to vagus nerve stimulation by enflurane or isoflurane or for the increase in response with atracurium are unknown. Pancuronium at lower doses increases the response most likely by blocking prejunctional muscarinic receptors (M2) that physiologically inhibit vagally mediated increases in pulmonary resistance.

Gas exchange and intrapulmonary distribution of ventilation during continuous-flow ventilation.

In 12 anesthetized paralyzed dogs, pulmonary gas exchange and intrapulmonary inspired gas distribution were compared between continuous-flow ventilation (CFV) and conventional mechanical ventilation (CMV). Nine dogs were studied while they were lying supine, and three dogs were studied while they were lying prone. A single-lumen catheter for tracheal insufflation and a double-lumen catheter for bilateral endobronchial insufflation [inspired O2 fraction = 0.4; inspired minute ventilation = 1.7 +/- 0.3 (SD) 1.kg-1.min-1] were evaluated. Intrapulmonary gas distribution was assessed from regional 133Xe clearances. In dogs lying supine, CO2 elimination was more efficient with endobronchial insufflation than with tracheal insufflation, but the alveolar-arterial O2 partial pressure difference was larger during CFV than during CMV, regardless of the type of insufflation. By contrast, endobronchial insufflation maintained both arterial PCO2 and alveolar-arterial O2 partial pressure difference at significantly lower levels in dogs lying prone than in dogs lying supine. In dogs lying supine, the dependent lung was preferentially ventilated during CMV but not during CFV. In dogs lying prone, gas distribution was uniform with both modes of ventilation. The alveolar-arterial O2 partial pressure difference during CFV in dogs lying supine was negatively correlated with the reduced ventilation of the dependent lung, which suggests that increased ventilation-perfusion mismatching was responsible for the increase in alveolar-arterial O2 partial pressure difference. The more efficient oxygenation during CFV in dogs lying prone suggests a more efficient matching of ventilation to perfusion, presumably because the distribution of blood flow is also nearly uniform.

Muscarinic M1 receptors mediate the increase in pulmonary resistance during vagus nerve stimulation in dogs.

The physiologic roles of the 2 muscarinic receptors (M1 and M2) in the vagal control of pulmonary resistance were studied by comparing the effects of pirenzepine (PZ, M1-blocker), gallamine (GAL, M2-blocker), and atropine (AT, M1- and M2-blocker) on the increase in pulmonary resistance (RL) and on the reduction in heart rate (HR) during bilateral cervical vagus nerve stimulation in 18 anesthetized (chloralose and urethane) and paralyzed (vecuronium) dogs. PZ, AT, and GAL all inhibited the reduction in HR during vagus nerve stimulation, although the inhibition required relatively high doses of PZ and GAL. AT and PZ inhibited the increase in RL during vagus nerve stimulation. The ratio of the dose needed to inhibit by 50% the HR response to the dose needed to inhibit by 50% the RL response was approximately 45:1 for PZ, 12:1 for AT, and less than 0.4:1 for GAL. Thus, compared with AT, PZ is a more selective blocker of vagally induced increases in RL, indicating that M1 receptors are present in the airway smooth muscle of intact anesthetized dogs. In the same dose range as that which caused the inhibition of the HR response, GAL had no consistent effect on the increase in RL during vagus nerve stimulation, indicating that M2 receptors do not mediate the increase in RL in intact anesthetized dogs.