Desflurane, Sevoflurane, and Isoflurane Impair Canine Left Ventricular-Arterial Coupling and Mechanical Efficiency

Background: The effects of desflurane, sevoflurane, and isoflurane on left ventricular-arterial coupling and mechanical efficiency were examined and compared in acutely instrumented dogs.

Methods: Twenty-four open-chest, barbiturate-anesthetized dogs were instrumented for measurement of aortic and left ventricular (LV) pressure (micromanometer-tipped catheter), dP/dtmax, and LV volume (conductance catheter). Myocardial contractility was assessed with the end-systolic pressure-volume relation (Ees) and preload recruitable stroke work (Msw) generated from a series of LV pressure-volume diagrams. Left ventricular-arterial coupling and mechanical efficiency were determined by the ratio of Ees to effective arterial elastance (Ea; the ratio of end-systolic arterial pressure to stroke volume) and the ratio of stroke work (SW) to pressure-volume area (PVA), respectively.

Results: Desflurane, sevoflurane, and isoflurane reduced heart rate, mean arterial pressure, and left ventricular systolic pressure. All three anesthetics caused similar decreases in myocardial contractility and left ventricular afterload, as indicated by reductions in Ees, Msw, and dP/dtmax and Ea, respectively. Despite causing simultaneous declines in Ees and Ea, desflurane decreased Ees /Ea (1.02+/-0.16 during control to 0.62+/-0.14 at 1.2 minimum alveolar concentration) and SW/PVA (0.51+/-0.04 during control to 0.43+/-0.05 at 1.2 minimum alveolar concentration). Similar results were observed with sevoflurane and isoflurane.     

Influence of Acidosis on Cardiotonic Effects of Milrinone

Background: The present study was designed to determine whether augmentation of cardiac performance by milrinone is affected by acidosis in in vivo canine and in vitro guinea pig preparations, and to elucidate a mechanism in relation to the cyclic adenosine monophosphate (cAMP) formation.

Methods: Halothane-anesthetized, ventilated dogs were randomly assigned to a control group (arterial pH [pHa] [nearly =] 7.4, base excess [BE] > -2 mM; n = 7), mild acidosis group (pHa [nearly =] 7.2, BE < -9 mM; n = 7), or severe acidosis group (pHa < 7, BE < -20 mM; n = 6). Arterial blood pressure, left ventricular pressure (including maximum rate of increase, LV dP/dtmax), and pulmonary blood flow (PBF) were measured. Acidosis was induced by transient hypoxia and maintained with hydrogen chloride infusion. Hemodynamic responses to milrinone infusions at 2 and 5 micro gram [center dot] kg sup -1 [center dot] min were then studied. In addition, left atria and right ventricular strips were dissected from guinea pig hearts and suspended in HEPES-Tyrode solution, with pH values adjusted to 7.4, 7, or 6.6. The concentration-response relation of isometric contractions for milrinone (10 sup -7 to 10 sup -4 M) and 8-bromo-cAP (10 sup -4 to 10 sup -3 M) were determined.

Results: In the control group of dogs, significant increases in LN dP/dtmax (2,674 +/- 822 to 3,999 +/- 1,016 mmHg/s [means +/- SD]) and PBF (2.04 +/- 0.98 to 2.44 +/- 0.96 l/min [means +/- SD]) were seen with a milrinone infusion of 5 micro gram [center dot] kg sup -1 [center dot] min sup -1. In the mild acidosis group, 5 micro gram [center dot] kg sup -1 min sup -1 milrinone also increased LV dP/dtmax and PBF. However, neither LV dP/dtmax nor PBF changed in the severe acidosis group. In in vitro experiments, milrinone exerted a positive inotropic effect in a concentration-dependent manner on the right ventricular preparations at pH 7.4, but not at pH 7 and 6.6, whereas no significant difference was observed in inotropic responses to 8-bromo-cAMP at pH values of 6.6, 7, and 7.4 on the right ventricular strips. In the right ventricular in vitro preparation, 10 sup -4 M milrinone was accompanied by a significant increase in intracellular cAMP content at a pH of 7.4 but not 7.     

A Brief Regional Ischemic-reperfusion Enhances Propofol-induced Depression in Left Ventricular Function of in situ Rat Hearts

Background: Propofol is short-acting intravenous general anesthetics that reduces cardiovascular hemodynamics. The effects of propofol on intrinsic myocardial contractility, however, remain debatable. The aim of the current study was to test the hypothesis that inhibitory effects of propofol on left ventricular (LV) contractility and mechanical work capability of in situ ejecting rat hearts are attenuated after a brief regional ischemia and reperfusion.

Methods: The authors obtained steady-state LV pressure-volume loops and intermittently obtained LV end-systolic pressure-volume relation and evaluated effects of propofol on LV function by end-systolic pressure (ESPmLVV), systolic pressure-volume area (PVAmLVV) at midrange LV volume (mLVV).

Results: Propofol (5.2 +/- 0.3~11.1 +/- 3.7 [mu]g[middle dot]ml-1) significantly decreased ESP0.08 to 78 +/- 12%~64 +/- 13% of prepropofol and PVA0.08 to 76 +/- 13%~63 +/- 16% of prepropofol in normal hearts, whereas propofol at a lower concentration (4.1 +/- 1.0 [mu]g/ml) did not. Although brief ischemic-reperfusion per se did not affect LV function, propofol after that, even at a lower concentration (4.1 +/- 1.0 [mu]g/ml), significantly decreased ESP0.08 to 70 +/- 27% of prepropofol and PVA0.08 to 68 +/- 33% of prepropofol. Pretreatment with a protein kinase C (PKC) inhibitor, bisindolylmaleimide reduced the propofol (4.1 +/- 1.0 [mu]g/ml)-induced greater decreases in ESP0.08 and PVA0.08 after brief ischemic-reperfusion to 94 +/- 33% and 92 +/- 39% of prepropofol. In the propofol-infused hearts after brief ischemic-reperfusion, protein kinase C-[epsilon] translocation to the nucleus-myofibril fraction was found.     

Effects of acute normovolemic hemodilution on ventriculoarterial coupling in dogs

BACKGROUND: Acute normovolemic hemodilution (ANH) causes a decrease in systemic vascular resistance. Similar to vasodilating drugs, ANH might modify ventriculoarterial coupling. Left ventricular elastance (Ees), effective arterial elastance (Ea), stroke work (SW), and pressure volume area (PVA) were used as indicators to examine the effects of ANH on this coupling. METHODS: After institutional approval eight dogs were anesthetized with isoflurane and subjected to measurements including aortic pressure, left ventricular (LV) pressure, and LV volume. Left ventricular volume was measured with a conductance catheter. Ees was determined as the slope of the end-systolic pressure-volume relationship. Ea was determined as the ratio of LV end-systolic pressure to stroke volume. Ventriculoarterial coupling was evaluated as the ratio of Ees to Ea. Mechanical efficiency, another criterion for ventriculoarterial coupling, was calculated as the ratio of SW to PVA. Data are expressed as mean+/-SD, and P<0.05 was considered significant. RESULTS: Normovolemic exchange of 50 ml kg-1 of blood for 6% hydroxyethyl starch (ANH50) reduced hemoglobin concentration from 12.8+/-3.0 g dl-1 to 6.4+/-1.3 g dl-1. Acute normovolemic hemodilution 50 did not change Ees significantly although it significantly decreased Ea. Left ventricular elastance/Ea did not change after ANH (1.0+/-0.4 at baseline and 1.2+/-0.5 at ANH50). Acute normovolemic hemodilution 50 significantly increased SW and PVA, preventing SW/PVA from changing significantly after ANH (0.57+/-0.10 at baseline and 0.62+/-0.14 at ANH50). CONCLUSION: Before ANH, ventriculoarterial coupling was so matched as to maximize SW at the expense of the work efficiency. This relation was preserved at ANH50.     

A Comparison of Left Ventricular Performance Indices Measured by Transesophageal Echocardiography with Automated Border Detection

Background: Automated border detection (ABD) allows semiautomated measurement of left ventricular (LV) areas. They can be combined with left ventricular pressure signals to generate pressure-area loops and pressure-dimension indices of contractility. This study compared conventional indices of ventricular performance (fractional area change [FAC] and circumferential fiber shortening [Vcfc]) with pressure-dimension indices of contractility. A secondary aim was to compare the effects of volatile anesthetics on the indices.

Methods: Using transesophageal echocardiography with automated border detection, FAC and Vcfc were obtained in 23 patients after cardiopulmonary bypass. Left ventricular pressures were obtained with a left ventricular catheter. Preload reduction by inferior vena caval occlusion was used to obtain end-systolic elastance (Ees), preload recruitable stroke force (PRSF), and dP/dtmax [middle dot] EDA-1 (EDA = end-diastolic area). In 11 patients, the measurements were repeated at 1 end-tidal minimum alveolar concentration of halothane or isoflurane. The results are expressed as mean +/- SD.

Results: After cardiopulmonary bypass, FAC was 31.1 +/- 7.9%, Vcfc was 0.6 +/- 0.2 circ [middle dot] s-1, Ees was 25.8 +/- 11.6 mmHg [middle dot] cm-2, PRSF was 60.8 +/- 26.6 mmHg, and dP/dtmax [middle dot] -EDA-1 was 245 +/- 123.4 mmHg [middle dot] s-1 [middle dot] cm-2. At 1 minimum alveolar concentration of a volatile anesthetic agent, FAC, Vcfc, and dP/dtmax [middle dot] EDA-1 remained unchanged. Significant decreases in Ees (19%) and PRSF (28%) were observed.     

The effects of propofol and midazolam on canine left ventricular contractility

Pronounced decrease in arterial blood pressure during propofol or midazolam infusion for sedation of critically ill patients, has raised the possibility that they have a direct negative inotropic action. Accordingly, in the current study, changes in the left ventricular (LV) contractility were examined during i.v. infusion of these two sedatives in anesthetized dogs. Myocardial contractility was assessed with the slope (Ees) of the LV end-systolic pressure-volume relationship and the slope (Msw) of the LV end-diastolic volume-stroke work relationship. Propofol was administered at 5, 10 and 20 mg.kg-1.h-1, and midazolam at 0.3, 0.6 and 1.2 mg.kg-1.h-1 over 60 min. Propofol caused dose-dependent decrease in Ees (55 +/- 7 during the low dose to 27 +/- 3 mmHg.ml-1 during the high dose, P < 0.05) and in Msw (91 +/- 8 during the low dose to 67 +/- 6 erg.cm-3 x 10(-3) during the high dose, P < 0.05). Midazolam, also, decreased in Ees and Msw significantly. No significant differences were observed between three different doses of midazolam. It is concluded that propofol shows the dose-dependent inhibition of myocardial contractility, but midazolam induces dose-independent inhibition.     

Ventricular energetics in endoventricular circular patch plasty for dyskinetic anterior left ventricular aneurysm

BACKGROUND: The endoventricular circular patch plasty (Dor procedure) applies to patients with a left ventricular dysfunction due to an ischemic dilated ventricle. In the present study, we analyzed left ventricular energetics in patients who underwent the Dor procedure. METHODS: We measured left ventricular contractility (end-systolic elastance; Ees), afterload (effective arterial elastance; Ea), and efficiency (ventriculoarterial coupling; Ea/Ees, and the ratio of stroke work and pressure-volume area; SW/PVA) based on the cardiac catheterization data before and after the Dor procedure in 8 patients with a postinfarction dyskinetic anterior left ventricular aneurysm. Concomitant procedures included coronary artery bypass grafting in all patients, mitral valve repair in one patient, and cryoablation in one patient. End-systolic elastance (Ees) and Ea were approximated as follows: Ees = mean arterial pressure/minimal left ventricular volume, and Ea = maximal left ventricular pressure/(maximal left ventricular volume-minimal left ventricular volume), and thereafter Ea/Ees and SW/PVA were calculated. The left ventricular volume was normalized with the body surface area. RESULTS: End-systolic elastance (Ees) increased after the Dor procedure (from 1.15 +/- 0.60 to 1.86 +/- 0.84 mm Hg x m2 x mL(-1), p < 0.01), thus resulting in an improvement in Ea/Ees and SW/PVA (from 2.94 +/- 1.11 to 1.64 +/- 0.49, p < 0.01, and from 0.426 +/- 0.110 to 0.559 +/- 0.082, p < 0.01, respectively), even though Ea did not substantially change (from 2.96 +/- 0.78 to 2.74 +/- 0.55 mm Hg x m2 x mL(-1), p = 0.4). CONCLUSIONS: Left ventricular contractility and efficiency improves after the Dor procedure in patients with a dyskinetic anterior left ventricular aneurysm. However, afterload does not change. The use of appropriate afterload-reducing therapy thus plays an especially important role in the management of patients who undergo the Dor procedure.     

Cardiovascular Effects of Propofol in Dogs with Dilated Cardiomyopathy

Background: The authors tested the hypothesis that propofol improves left ventricular diastolic function in dogs with dilated cardiomyopathy by reducing left ventricular preload and afterload.

Methods: Seven dogs were instrumented for left ventricular and aortic pressures, aortic blood flow, and subendocardial segment length. Left ventricular afterload and contractility were quantified with aortic input impedance and preload recruitable stroke work, respectively. Diastolic function was evaluated with a time constant of left ventricular relaxation (tau); segment-lengthening velocities and time-velocity integrals during early left ventricular filling (dL/dtE and TVI-E, respectively) and atrial systole (dL/dtA and TVI-A, respectively); and a regional chamber stiffness constant (K). Dogs were paced at 240 beats/min for 18 +/- 3 days, and hemodynamics were recorded in sinus rhythm in the conscious state. Anesthesia was induced with propofol (5 mg/kg) and maintained with propofol infusions at 25, 50, and 100 mg [center dot] kg sup -1 [center dot] h sup -1, and hemodynamics were recorded after 15 min of equilibration at each dose.

Results: Propofol decreased mean arterial pressure, left ventricular end-diastolic pressure, and K but did not change heart rate. Propofol reduced total arterial resistance and increased total arterial compliance derived from aortic input impedance. Propofol also reduced preload recruitable stroke work. The lowest dose of propofol decreased tau. Propofol decreased dL/dtE and TVI-E and reduced the dL/dt-E/A and TVI-E/A ratios.     

Sex-related Differences in the Influence of Morphine on Ventilatory Control in Humans

Background: Opiate agonists have different analgesic effects in male and female patients. The authors describe the influence of sex on the respiratory pharmacology of the micro-receptor agonist morphine.

Methods: The study was placebo-controlled, double-blind, and randomized. Steady-state ventilatory responses to carbon dioxide and responses to a step into hypoxia (duration, 3 min; oxygen saturation, [approximately] 82%; end-tidal carbon dioxide tension, 45 mmHg) were obtained before and during intravenous morphine or placebo administration (bolus dose of 100 micro gram/kg, followed by a continuous infusion of 30 micro gram [center dot] kg sup -1 [center dot] h sup -1) in 12 men and 12 women.

Results: In women, morphine reduced the slope of the ventilatory response to carbon dioxide from 1.8 +/- 0.9 to 1.3 +/- 0.7 l [center dot] min sup -1 [center dot] mmHg sup -1 (mean +/- SD; P < 0.05), whereas in men there was no significant effect (control = 2.0 +/- 0.4 vs. morphine = 1.8 +/- 0.4 l [center dot] min sup -1 [center dot] mmHg sup -1). Morphine had no effect on the apneic threshold in women (control = 33.8 +/- 3.8 vs. morphine = 35.3 +/- 5.3 mmHg), but caused an increase in men from 34.5 +/- 2.3 to 38.3 +/- 3 mmHg, P < 0.05). Morphine decreased hypoxic sensitivity in women from 1.0 +/- 0.5 l [center dot] min sup -1 [center dot] % sup -1 to 0.5 +/- 0.4 l [center dot] min sup -1 [center dot] % sup -1 (P < 0.05) but did not cause a decrease in men (control = 1.0 +/- 0.5 l [center dot] min sup -1 [center dot] % sup -1 vs. morphine = 0.9 +/- 0.5 l [center dot] min sup -1 [center dot] % sup -1). Weight, lean body mass, body surface area, and calculated fat mass differed between the sexes, but their inclusion in the analysis as a covariate revealed no influence on the differences between men and women in morphine-induced changes.     

Mechanisms whereby Propofol Mediates Peripheral Vasolidation in Humans: Sympathoinhibition or Direct Vascular Relaxation?

Background: Anesthetic induction and maintenance with propofol are associated with decreased blood pressure that is, in part, due to decreased peripheral resistance. Several possible mechanisms whereby propofol could reduce peripheral resistance include a direct action of propofol on vascular smooth muscle, an inhibition of sympathetic activity to the vasculature, or both. This study examined these two possibilities in humans by measuring the forearm vascular responses to infusions of propofol into the brachial artery (study 1) and by determining the forearm arterial and venous responses to systemic (intravenous) infusions of propofol after sympathetic denervation of the forearm by stellate blockade (study 2).

Methods: Bilateral forearm venous occlusion piethysmography was used to examine forearm vascular resistance (FVR) and forearm vein compliance (FVC). Study 1 used infusion of intralipid (time control) and propofol at rates between 83 and 664 micro gram/min into the brachial artery of 11 conscious persons and compared responses to arterial infusions of sodium nitroprusside (SNP) at 0.3, 3.0, and 10 micro gram/min. Venous blood from the infusion arm was assayed for plasma propofol concentrations. In study 2, after left stellate block (12 ml 0.25% bupivacaine + 1% lidocaine), six participants were anesthetized and maintained with propofol infusions of 125 and 200 micro gram [centered dot] kg sup -1 [centered dot] min sup -1. Simultaneous right forearm (unblocked) blood flow dynamics served as the time control. In three additional conscious participants, intrabrachial artery infusions of SNP and nitroglycerin, both at 10 micro gram/min, were performed before and after stellate blockade of the left forearm to determine whether the sympathetically denervated forearm vessels could dilate beyond the level produced by denervation alone.

Results: In study 1, infusion of intralipid or propofol into the brachial artery did not change FVR or FVC. Sodium nitroprusside significantly decreased FVR in a dose-dependent manner by 22 +/- 5%, 65 +/- 3%, and 78 +/- 2% (mean +/- SEM) but did not change FVC. During the incremental propofol infusions, plasma propofol concentrations increased from 0.2 to 10.1 micro gram/ml and averaged 7.4 +/- 1.1 micro gram/ml during the highest infusion rate. In study 2, stellate ganglion blockade decreased FVR by 50 +/- 6% and increased FVC by 58 +/- 10%. Propofol anesthesia at 125 and 200 micro gram [centered dot] kg sup -1 [centered dot] min sup -1 progressively reduced mean arterial pressure. In the arm with sympathetic denervation, FVR and FVC showed no further changes during propofol anesthesia, whereas in the control arm FVR significantly decreased by 41 +/- 9% and 42 +/- 7%, and FVC increased significantly by 89 +/- 27% and 85 +/- 32% during 125 and 200 micro gram [centered dot] kg sup -1 [centered dot] min sup -1 infusions of propofol, respectively. In the three additional conscious participants, intraarterial infusion of SNP and nitroglycerin (TNG) after the stellate blockade resulted in a further decrease of FVR and a further increase of FVC.     

Positron Emission Tomography Study of Regional Cerebral Metabolism in Humans during Isoflurane Anesthesia

Background: Although the anesthetic effects of the intravenous anesthetic agent propofol have been studied in the living human brain using brain imaging technology, the nature of the anesthetic state evident in the human brain during inhalational anesthesia remains unknown. To examine this issue, the authors studied the effects of isoflurane anesthesia on human cerebral glucose metabolism using positron emission tomography (PET).

Methods: Five volunteers each underwent two PET scans; one scan assessed awake-baseline metabolism and the other scan assessed metabolism during isoflurane anesthesia titrated to the point of unresponsiveness (means +/- SD; expired = 0.5 +/- 0.1%). Scans were obtained with a GE2048 scanner (4.5-mm resolution-FWHM) using the18 fluorodeoxyglucose technique.

Results: Awake whole-brain glucose metabolism averaged 6.9 +/- 1.5 mg [center dot] 100 g sup -1 [center dot] min sup -1 (means +/- SD). Isoflurane reduced whole-brain metabolism 46 +/- 11% to 3.6 +/- 0.3 mg [center dot] 100 g sup -1 [center dot] min sup -1 (P less or equal to 0.005). Regional metabolism decreased fairly uniformly throughout the brain, and no evidence of any regional metabolic increases were found in any brain region for any participant. A region-of-interest analysis showed that the pattern of regional metabolism evident during isoflurane anesthesia was not significantly different from that seen when participants were awake.     

A brief regional ischemic-reperfusion enhances propofol-induced depression in left ventricular function of in situ rat hearts

BACKGROUND: Propofol is short-acting intravenous general anesthetics that reduces cardiovascular hemodynamics. The effects of propofol on intrinsic myocardial contractility, however, remain debatable. The aim of the current study was to test the hypothesis that inhibitory effects of propofol on left ventricular (LV) contractility and mechanical work capability of in situ ejecting rat hearts are attenuated after a brief regional ischemia and reperfusion. METHODS: The authors obtained steady-state LV pressure-volume loops and intermittently obtained LV end-systolic pressure-volume relation and evaluated effects of propofol on LV function by end-systolic pressure (ESPmLVV), systolic pressure-volume area (PVAmLVV) at midrange LV volume (mLVV). RESULTS: Propofol (5.2 +/- 0.3 approximately 11.1 +/- 3.7 microg.ml) significantly decreased ESP0.08 to 78 +/- 12% approximately 64 +/- 13% of prepropofol and PVA0.08 to 76 +/- 13%approximately 63 +/- 16% of prepropofol in normal hearts, whereas propofol at a lower concentration (4.1 +/- 1.0 microg/ml) did not. Although brief ischemic-reperfusion per se did not affect LV function, propofol after that, even at a lower concentration (4.1 +/- 1.0 microg/ml), significantly decreased ESP0.08 to 70 +/- 27% of prepropofol and PVA0.08 to 68 +/- 33% of prepropofol. Pretreatment with a protein kinase C (PKC) inhibitor, bisindolylmaleimide reduced the propofol (4.1 +/- 1.0 microg/ml)-induced greater decreases in ESP0.08 and PVA0.08 after brief ischemic-reperfusion to 94 +/- 33% and 92 +/- 39% of prepropofol. In the propofol-infused hearts after brief ischemic-reperfusion, protein kinase C-epsilon translocation to the nucleus-myofibril fraction was found. CONCLUSION: In contrast to the study hypothesis, brief ischemic-reperfusion enhanced the inhibitory effects of propofol on LV systolic function; this enhancement is attributable to activation of protein kinase C.     

A Comparison of Remifentanil and Morphine Sulfate for Acute Postoperative Analgesia after Total Intravenous Anesthesia with Remifentanil and Propofol

Background: The transition from remifentanil intraoperative anesthesia to postoperative analgesia must be planned carefully due to the short duration of action (3-10 min) of remifentanil hydrochloride, a potent, esterase-metabolized micro-opioid agonist. This study compared the efficacy and safety of transition regimens using remifentanil or morphine sulfate for immediate postoperative pain relief in patients who had surgery under general anesthesia with remifentanil/propofol.

Methods: One hundred fifty patients who had received open-label remifentanil and propofol for intraoperative anesthesia participated in this multicenter, double-blind, double-dummy study and were randomly assigned to either the remifentanil (R) group or the morphine sulfate (M) group. Twenty minutes before the anticipated end of surgery, the propofol infusion was decreased by 50%, and patients received either a placebo bolus (R group) or a bolus of 0.15 mg/kg morphine (M group). At the end of surgery, the propofol and remifentanil maintenance infusions were discontinued and the analgesic infusion was started: either 0.1 micro gram [center dot] kg sup -1 [center dot] min sup -1 remifentanil (R group) or placebo analgesic infusion (M group). During the 25 min after tracheal extubation, remifentanil titrations in increments of 0.025 micro gram [center dot] kg sup -1 [center dot] min sup -1 and placebo boluses (R group), or 2 mg intravenous morphine boluses and placebo rate increases (M group) were administered as necessary at 5-min intervals to control pain. Patients received the 0.075 mg/kg intravenous morphine bolus (R group) or placebo (M group) at 25 and 30 min after extubation, and the analgesic infusion was discontinued at 35 min. From 35 to 65 minutes after extubation, both groups received 2-6 mg open-label morphine analgesia every 5 min as needed.

Results: Successful analgesia, defined as no or mild pain with adequate respiration (respiratory rate [RR] >or= to 8 breaths/min and pulse oximetry >or= to 90%), was achieved in more patients in the R group than in the M group (58% vs. 33%, respectively) at 25 min after extubation (P < 0.05). The median remifentanil rate for successful analgesia was 0.125 micro gram [center dot] kg sup -1 [center dot] min sup -1 (range, 0.05-0.23 micro gram [center dot] kg sup -1 [center dot] min sup -1), and the median number of 2-mg morphine boluses used was 2 (range, 0-5 boluses). At 35 min after extubation, >or= to 74% of patients in both groups experienced moderate to severe pain. Median recovery times from the end of surgery were similar between groups. Transient respiratory depression, apnea, or both were the most frequent adverse events (14% for the R group vs. 6% for the M group; P > 0.05).     

Comparison of Remifentanil and Fentanyl in Patients Undergoing Craniotomy for Supratentorial Space-occupying Lesions

Background: Remifentanil hydrochloride is an ultra-short-acting, esterase-metabolized micro-opioid receptor agonist. This study compared the use of remifentanil or fentanyl during elective supratentorial craniotomy for space-occupying lesions.

Methods: Sixty-three adults gave written informed consent for this prospective, randomized, double-blind, multiple-center trial. Anesthesia was induced with thiopental, pancuronium, nitrous oxide/oxygen, and fentanyl (n = 32; 2 micro gram [center dot] kg [center dot] sup -1 min sup -1) or remifentanil (n = 31; 1 micro [center dot] kg sup -1 [center dot] min sup -1). After tracheal intubation, infusion rates were reduced to 0.03 micro gram [center dot] kg sup -1 [center dot] min sup -1 (fentanyl) or 0.2 micro gram [center dot] kg sup -1 [center dot] min sup -1 (remifentanil) and then adjusted to maintain anesthesia and stable hemodynamics. Isoflurane was given only after specified infusion rate increases had occurred. At the time of the first burr hole, intracranial pressure was measured in a subset of patients. At bone flap replacement either saline (fentanyl group) or remifentanil ([nearly equal] 0.2 micro gram [center dot] kg sup -1 [center dot] min sup -1) were infused until dressing completion. Hemodynamics and time to recovery were monitored for 60 min. Analgesic requirements and nausea and vomiting were observed for 24 h. Neurological examinations were performed before operation and on postoperative days 1 and 7.

Results: Induction hemodynamics were similar. Systolic blood pressure was greater in the patients receiving fentanyl after tracheal intubation (fentanyl = 127 +/- 18 mmHg; remifentanil = 113 +/- 18 mmHg; P = 0.004). Intracranial pressure (fentanyl = 14 +/- 13 mmHg; remifentanil = 13 +/- 10 mmHg) and cerebral perfusion pressure (fentanyl = 76 +/- 19 mmHg; remifentanil = 78 +/- 14 mmHg) were similar. Isoflurane use was greater in the patients who received fentanyl. Median time to tracheal extubation was similar (fentanyl = 4 min: range = -1 to 40 min; remifentanil = 5 min: range = 1 to 15 min). Seven patients receiving fentanyl and none receiving remifentanil required naloxone. Postoperative systolic blood pressure was greater (fentanyl = 134 +/- 16 mmHg; remifentanil = 147 +/- 15 mmHg; P = 0.001) and analgesics were required earlier in patients receiving remifentanil. Incidences of nausea and vomiting were similar.     

Single-beat Estimation of Ventricular End-systolic Elastance-Effective Arterial Elastance as an Index of Ventricular Mechanoenergetic Performance

Background: The ratio of ventricular end-systolic elastance (Ees) to effective arterial elastance (Ea) is known to reflect not only ventricular mechanical performance but also energetic performance. Despite these useful features, technical difficulties associated with estimating Ees make the clinical application of Ees/Ea impractical. We developed a framework to estimate Ees/Ea without measuring ventricular volume or altering the loading condition.

Methods: To achieve this goal, we approximated the ventricular time-varying elastance curve with two straight lines, one for the isovolumic phase and the other for the ejection phase, and characterized the curve with the slope ratio, k, of these two straight lines. Using the concept of the pressure-volume relationship, Ees/Ea is algebraically expressed as Ees/Ea = Pad/Pes (1 + k [middle dot] ET/PEP) - 1, where Pes is end-systolic pressure, Pad is aortic diastolic pressure, ET is ejection time, and PEP is pre-ejection period. In 11 anesthetized dogs, we recorded arterial and ventricular pressures and ventricular volume and estimated Ees and Ea under various contractile states and loading conditions.

Results: An empirical relation between k and Ees/Ea was found as k = 0.53 (Ees/Ea)0.51. Simultaneous solution of these two equations yielded Ees/Ea as a function of Pad/Pes and ET/PEP. The estimated Ees/Ea values correlated well with the measured Ees/Ea values ([Measured Ees/Ea] = 0.96 [Estimated Ees/Ea] + 0.098, r = 0.925, SEE = 0.051).     

Sevoflurane but Not Propofol Preserves Myocardial Function in Coronary Surgery Patients

Background: Sevoflurane has been shown to protect against myocardial ischemia and reperfusion injury in animals. The present study investigated whether these effects were clinically relevant and would protect left ventricular (LV) function during coronary surgery.

Methods: Twenty coronary surgery patients were randomly assigned to receive either target-controlled infusion of propofol or inhalational anesthesia with sevoflurane. Except for this, anesthetic and surgical management was the same in all patients. A high-fidelity pressure catheter was positioned in the left ventricle and the left atrium. LV response to increased cardiac load, obtained by leg elevation, was assessed before and after cardiopulmonary bypass (CPB). Effects on contraction were evaluated by analysis of changes in dP/dtmax. Effects on relaxation were assessed by analysis of the load dependence of myocardial relaxation (R = slope of the relation between time constant [tau] of isovolumic relaxation and end-systolic pressure). Postoperative concentrations of cardiac troponin I were followed during 36 h.

Results: Before CPB, leg elevation slightly increased dP/dtmax in the sevoflurane group (5 +/- 3%), whereas it remained unchanged in the propofol group (1 +/- 6%). After CPB, leg elevation resulted in a decrease in dP/dtmax in the propofol group (-5 +/- 4%), whereas the response in the sevoflurane group was comparable to the response before CPB (5 +/- 4%). Load dependence of LV pressure fall (R) was similar in both groups before CPB. After CPB, R was increased in the propofol group but not in the sevoflurane group. Troponin I concentrations were significantly lower in the sevoflurane than in the propofol group.     

Remifentanil versus Remifentanil/midazolam for Ambulatory Surgery during Monitored Anesthesia Care

Background: This study was designed to define the appropriate dose of remifentanil hydrochloride alone or combined with midazolam to provide satisfactory comfort and maintain adequate respiration for a monitored anesthesia care setting.

Methods: One hundred fifty-nine patients scheduled for outpatient surgery participated in this multicenter, double-blind study. Patients were randomly assigned to one of two groups: remifentanil, 1 micro gram/kg, given over 30 s followed by a continuous infusion of 0.1 micro gram [center dot] kg sup -1 [center dot] min sup -1 (remifentanil); remifentanil, 0.5 micro gram/kg, given over 30 s followed by a continuous infusion of 0.05 micro gram [center dot] kg sup -1 [center dot] min sup -1 (remifentanil + midazolam). Five minutes after the start of the infusion, patients received a loading dose of saline placebo (remifentanil) or midazolam, 1 mg, (remifentanil + midazolam). If patients were not oversedated, a second dose of placebo or midazolam, 1 mg, was given. Remifentanil was titrated (in increments of 50% from the initial rate) to limit patient discomfort or pain intraoperatively, and the infusion was terminated at the completion of skin closure.

Results: At the time of the local anesthetic, most patients in the remifentanil and remifentanil + midazolam groups experienced no pain (66% and 60%, respectively) and no discomfort (66% and 65%, respectively). The final mean (+/- SD) remifentanil infusion rates were 0.12 +/- 0.05 micro gram [center dot] kg sup -1 [center dot] min sup -1 (remifentanil) and 0.07 +/- 0.03 micro gram [center dot] kg sup -1 [center dot] min sup -1 (remifentanil + midazolam). Fewer patients in the remifentanil + midazolam group experienced nausea compared with the remifentanil group (16% vs. 36%, respectively; P < 0.05). Four patients (5%) in the remifentanil group and two patients (2%) in the remifentanil + midazolam group experienced brief periods of oxygen desaturation (SpO2 < 90%) and hypoventilation (< 8 breaths/min).     

Length-dependent Regulation of Left Ventricular Function in Coronary Surgery Patients

Background: Load-dependent impairment of left ventricular (LV) function was observed after leg elevation in a subgroup of coronary surgery patients. The present study investigated underlying mechanisms by comparing hemodynamic effects of an increase in LV systolic pressures with leg elevation to effects of a similar increase in systolic pressures with phenylephrine.

Methods: The study was performed in patients undergoing elective coronary surgery prior to cardiopulmonary bypass. High-fidelity LV pressure tracings (n = 25) and conductance LV volume data (n = 10) were obtained consecutively during leg elevation and after phenylephrine administration (5 [micro sign]g/kg).

Results: Leg elevation resulted in a homogeneous increase in end-diastolic volume. The change in stroke volume (SV), stroke work (SW) and dP/dtmax was variable, with an increase in some patients but no change or a decrease in other patients. For a matched increase in systolic pressures, phenylephrine increased SW and dP/dtmax in all patients with no change in SV. Load dependence of relaxation (slope R of the [Greek small letter tau]-end-systolic pressure relation) was inversely related for changes in SV, SW, and dP/dtmax with leg elevation but not with phenylephrine.     

Selective Pulmonary Vasodilation Induced by Aerosolized Zaprinast

Background: Zaprinast, an inhibitor of guanosine-3',5'-cyclic monophosphate (cGMP)-selective phosphodiesterase, augments smooth muscle relaxation induced by endothelium-dependent vasodilators (including inhaled nitric oxide [NO]). The present study was designed to examine the effects of inhaled nebulized zaprinast, alone, and combined with inhaled NO.

Methods: Eight awake lambs with U46619-induced pulmonary hypertension sequentially breathed two concentrations of NO (5 and 20 ppm), followed by inhalation of aerosols generated from solutions containing four concentrations of zaprinast (10, 20, 30, and 50 mg/ml). The delivered doses of nebulized zaprinast at each concentration (mean +/- SD) were 0.23 +/- 0.06, 0.49 +/- 0.14, 0.71 +/- 0.24, and 1.20 +/- 0.98 mg [center dot] kg sup -1 [center dot] min sup -1, respectively. Each lamb also breathed NO (5 and 20 ppm) and zaprinast (0.23 +/- 0.06 mg [center dot] kg sup -1 [center dot] min sup -1) in combination after a 2-h recovery period.

Results: Inhaled NO selectively dilated the pulmonary vasculature. Inhaled zaprinast selectively dilated the pulmonary circulation and potentiated and prolonged the pulmonary vasodilating effects of inhaled NO. The net transpulmonary release of cGMP was increased by inhalation of NO, zaprinast, or both. The duration of the vasodilation induced by zaprinast inhalation was greater than that induced by NO inhalation.     

Mechanical restitution curves reflect post-ischemic stunning in pigs

OBJECTIVES: The time constant of mechanical restitution (T(MRC)), proposed to reflect changes in calcium release and uptake, has been shown to increase in left ventricular (LV) failure. In this study, we tested the hypothesis that T(MRC) also can identify post-ischemic, reversible LV dysfunction (stunning). DESIGN: Stunning was induced by a series of left main coronary artery occlusions in eight anesthetized open chest pigs. Left ventricular pressure-volume relations were assessed using a pressure-volume catheter during right atrial pacing. Mechanical restitution curves (MRCs) were constructed using two different measures of contractile response: maximal first derivative of pressure (CR(dP/dtmax)) and stroke work (CR(SW)). RESULTS: Mean arterial pressure, stroke volume and dP/dtmax were decreased 30 min after stunning. Slopes of end-systolic pressure volume relation and preload recruitable stroke work, however, showed no significant changes after stunning. For MRCs based on CR(dP/dtmax), T(MRC) increased in all eight animals. Using CR(SW), T(MRC) increased in seven out of eight pigs. CONCLUSIONS: Ischemia-reperfusion induce changes in MRCs based on CR(dP/dtmax), and CR(SW). The MRC concept may have potential as a clinical left ventricular performance index.