The effect of distance from injection site to the brainstem using spinal sufentanil.

BACKGROUND AND OBJECTIVES: Intrathecal (IT) sufentanil is commonly used in parturients to provide rapid onset of labor analgesia without motor block. This practice, although widely used, has been associated with severe respiratory depression in some patients. The mechanism of this respiratory depression is unclear, however, rapid cephalad movement and interaction with parenteral opioids are 2 frequently cited explanations for this complication. Because this complication has occurred only in women with heights between 150 and 157 cm, we elected to study the effect of the distance from injection site to the cisterna magna (CM) on peak brainstem cerebrospinal fluid (CSF) concentrations. METHODS: Ten adult ewes were injected with IT sufentanil (0.3 microg/kg) at a mean distance of either 71 cm (65 to 78 cm) from the brainstem (pelvic group) or 37 cm (34 to 42 cm) from the brainstem (thoracic group). CSF was then sampled at 5-minute intervals from the CM. RESULTS: Measurable CM concentrations of sufentanil were noted in the brainstem at 20 and 25 minutes, respectively, for the thoracic and the pelvic groups. Peak sufentanil concentrations from the thoracic group were nearly 10-fold higher (0.553 +/- 0.43 ng/mL) compared with the pelvic group (0.064 +/- 0.002 ng/mL) when measured in the CM (P =.023). CONCLUSIONS: Our results suggest that sufentanil migrates relatively large distances in the IT space. Injection site (distance from the brainstem) appears to be a prominent factor in determining brainstem concentrations and subsequent respiratory depression after spinal administration. Reg Anesth Pain Med 2001;26:306-309.

Compartmental modeling of technetium-99m-labeled teboroxime with dynamic single-photon emission computed tomography: comparison with static thallium-201 in a canine model.

UNLABELLED: Di Bella EVR, Ross SG, Kadrmas DJ, et al. Compartmental modeling of technetium-99m-labeled teboroxime with dynamic single-photon emission computed tomography: Comparison with static thallium-201 in a canine model. Invest Radiol 2001;36:178-185. RATIONALE AND OBJECTIVES: A compartmental modeling approach to deriving kinetic parameters from a time series of single-photon emission computed tomography (SPECT) images of technetium-99m-labeled (99mTc-) teboroxime may have value for semiquantitative assessment of myocardial perfusion. This study investigated the value of the kinetic parameters derived from a two-compartment model of 99mTc-teboroxime for measuring myocardial perfusion and compared it with static thallium-201 (201Tl) uptake and microsphere-measured blood flow in dogs. METHODS: Experiments were successfully conducted in 9 of 11 open-chest dogs. During adenosine stress, a single complete set of projections of 201Tl uptake was acquired. 99mTc-teboroxime was then injected during adenosine stress, and a complete set of projections was acquired every 5.7 seconds for 17 minutes. Resting studies were performed on 4 of the animals. All of the projection sets were reconstructed with an iterative algorithm and incorporated corrections for attenuation and the geometric response of the collimators. Regional kinetic parameters (washin and washout) were determined semiautomatically from the time series of reconstructed 99mTc-teboroxime images and registered with microsphere data. Regional washin estimates were compared with 201Tl intensities and myocardial blood flows determined from microspheres. RESULTS: Optimally scaled 99mTc-teboroxime washin parameters and 201Tl uptakes were correlated with microsphere-determined blood flows (r = 0.91, y = 0. 99x + 0.01, and r = 0.92, y = 0.88x + 0.28, respectively). In six of the studies, the left anterior descending coronary artery was occluded, and stress occluded-to-normal (O/N) ratios were calculated. The O/N ratios were 0.32 +/- 0.17 as determined from microspheres injected with 201Tl and 0.38 +/- 0.29 from microspheres injected with 99mTc-teboroxime (P = NS). The O/N ratios were 0.48 +/- 0.16 for static 201Tl uptake and 0.27 +/- 0.21 for 99mTc-teboroxime washin (P < 0.05). CONCLUSIONS: Both 201Tl uptake and 99mTc-teboroxime kinetic parameters were well correlated with flow. The 99mTc-teboroxime washin parameters offer semiquantitative flow values and provide greater defect contrast than can be obtained with 201Tl uptake values.

Influence of hemorrhagic shock on remifentanil: a pharmacokinetic and pharmacodynamic analysis.

BACKGROUND: Hemorrhagic shock is known to alter significantly the pharmacokinetics of fentanyl, an opioid that requires delivery to the liver for metabolism. The authors hypothesized that the pharmacokinetics and pharmacodynamics of remifentanil, an esterase metabolized opioid that does not require delivery to a metabolic organ, would be altered less by hemorrhagic shock that those of fentanyl. METHODS: Sixteen pigs were assigned randomly to control and shock groups. The shock group was bled using an isobaric hemorrhage model. Remifentanil 10 microg x kg(-1) x min(-1) was infused for 10 min to both groups. Arterial samples were collected for remifentanil concentration assay. Pharmacokinetic parameters were estimated using a three-compartment model. The electroencephalogram spectral edge was used as a measure of drug effect. The pharmacodynamics were characterized using a sigmoid inhibitory maximal effect model. RESULTS: Remifentanil blood levels were higher in the shocked group. The central clearance was slower and the central compartment was smaller in shocked animals. No difference between groups was observed in the magnitude or time course of the remifentanil-induced decrease in spectral edge. CONCLUSIONS: Hemorrhagic shock altered the pharmacokinetics of remifentanil, suggesting that less remifentanil would be required to maintain a target plasma concentration. However, because of its rapid metabolism, the impact of hemorrhagic shock on the concentration decline of remifentanil after termination of the infusion was minimal. Hemorrhagic shock did not alter the pharmacodynamics of remifentanil.

Partial CO2 rebreathing indirect Fick technique for non-invasive measurement of cardiac output.

OBJECTIVE: Evaluation in animals of a non-invasive and continuous cardiac output monitoring system based on partial carbon-dioxide (CO2) rebreathing indirect Fick technique. METHODS: We have developed a non-invasive cardiac output (NICO) monitoring system, based on the partial rebreathing method. The partial rebreathing technique employs a differential form of the Fick equation for calculating cardiac output (QT) using non-invasive measurements. Changes in CO2 elimination (deltaVCO2) and partial pressure of end-tidal CO2 (deltaPETCO2) in response to a brief period of partial rebreathing are used to measure pulmonary capillary blood flow (Q(PCBF)). A non-invasive estimate of anatomic and intrapulmonary shunt fraction (Q(S)/Q(T)), based on oxygen saturation from pulse oximetry (SpO2) and inspired oxygen concentration (FIO2), is added to compute total cardiac output [Q(T) = Q(PCBF)/(1 - Q(S)/Q(T))]. The performance of the NICO was compared with iced 5% dextrose bolus thermodilution cardiac output (TDco) measurements in 6 dogs. Cardiac output was varied using dobutamine, and halothane, and by clamping of the inferior vena cava. Two hundred and forty-six (n = 246) paired measurements of TDco and NICO over a range of cardiac outputs (TDco range = 0.60-8.87 l/min) were compared using Bland-Altman analysis and weighted correlation coefficient. RESULTS: The Bland-Altman technique yielded a NICO precision of +/- 0.70 l/min (13.8%) with a mean bias of -0.07 l/min (-1.4%) compared to TDco. The weighted correlation coefficient between TDco and NICO values was: r = 0.93 (n = 246). CONCLUSION: The partial CO2 rebreathing technique for measurement of cardiac output is non-invasive, automated, and based on the well accepted Fick principle. The limits of agreement between NICO and TDco is within the recommended value for NICO to be a clinically acceptable method for cardiac output measurement. The results of this canine study show that NICO performed as well, and in some cases better, than other currently available non-invasive cardiac output techniques over a wide range of cardiac outputs.

Fentanyl pharmacokinetics in hemorrhagic shock: a porcine model.

BACKGROUND: It is common clinical practice to administer reduced doses of opioid to patients suffering from hemorrhagic shock to minimize adverse hemodynamic consequences and to prevent prolonged opioid effect However, the scientific foundation supporting this practice is not well established. The aim of this study was to test the hypothesis that hemorrhagic shock alters both the distribution and clearance of opioids using fentanyl in a porcine isobaric hemorrhage model. METHODS: Eighteen pigs were randomized to shock or control groups. The animals in the shock group were subjected to hemorrhage using an isobaric method. Pigs in both groups received fentanyl (50 microg/kg) intravenously over 5 min. Frequent arterial blood samples were obtained for radioimmunoassay. Each animal's pharmacokinetic parameters were estimated by fitting a three-compartment model to the concentration versus time data Nonlinear mixed-effects population pharmacokinetic models examining the influence of mean arterial pressure and cardiac index were also constructed. Clinical simulations using the final population model were performed. RESULTS: The shock cohort reached substantially higher fentanyl concentrations. The shock group's central clearance and central- and second-compartment distribution volumes were significantly reduced. The most useful population model scaled all pharmacokinetic parameters to mean arterial pressure. The simulations illustrated that hemorrhagic shock results in higher fentanyl concentrations for any given dosage scheme. CONCLUSION: The essential finding of the study is that fentanyl pharmacokinetics are substantially altered by hemorrhagic shock. The reduced opioid requirement commonly observed during hemorrhagic shock is at least partially attributable to pharmacokinetic mechanisms.

The effect of prior dural puncture on cerebrospinal fluid sufentanil concentrations in sheep after the administration of epidural sufentanil.

UNLABELLED: Sufentanil is a highly lipid soluble opioid that provides potent analgesia when administered in the subarachnoid space. Unfortunately, the penetration of sufentanil into the cerebrospinal fluid (CSF) after epidural administration is poor, and limits its effectiveness for epidural analgesia. Dural puncture may enhance the movement of epidural sufentanil into the subarachnoid space and increase its effectiveness. To determine whether the administration of epidural sufentanil adjacent to a dural puncture results in significantly greater CSF concentrations, 18 adult ewes were studied. Animals in the control group had an epidural catheter placed at the superior border of the pelvis without dural puncture. Animals in the study group had an epidural catheter placed, followed by a dural puncture performed using an 18-gauge Touhy needle. The dural puncture was performed one interspace cephalad to the epidural catheter. One hour after dural puncture, each animal received a loading dose of 0.35 microg/kg of sufentanil (5 microg/mL) through the epidural catheter, followed by an infusion of epidural sufentanil 0.15 microg x kg(-1) x h(-1) for a period of 4 h. After 4 h, CSF was sampled from a site one interspace caudad to the epidural catheter as well as at the cisterna magna. The mean CSF concentration of sufentanil at the level of the pelvis for animals with a dural puncture was 12.1 +/- 3.0 ng/mL compared with 1.8 ng/mL in controls with intact dura. Sufentanil concentrations at the cisterna magna were below the level of detection (0.08 ng/mL) for all animals in both groups. We conclude that an 18-gauge dural puncture significantly increases movement of sufentanil from the epidural to the intrathecal space. This increase in sufentanil concentration at the level of the pelvis was not associated with detectable levels of sufentanil at the brainstem. IMPLICATIONS: This study addresses the effect of dural puncture on spinal fluid concentrations of sufentanil after epidural administration. A sheep model was used to measure drug concentrations in the spinal fluid at the levels of the pelvis and brainstem after epidural administration. Dural puncture significantly enhanced movement of sufentanil into the spinal fluid at the level of the pelvis, but brainstem concentrations were below the level of detection. Analgesic concentrations of spinal sufentanil in the clinical setting, as well as brainstem concentrations associated with respiratory depression, have yet to be defined.

Evaluation in volunteers of the VIA V-ABG automated bedside blood gas, chemistry, and hematocrit monitor.

OBJECTIVE: To evaluate the VIA V-ABG (VIA Medical Corp.) point-of-care blood gas and chemistry monitor in healthy human volunteers, with particular emphasis on the measurement of blood gases. METHODS: Experimental conditions were varied by intermittently subjecting volunteers to either isocapnic hypercapnia (end-tidal (ET), PETCO2 = 50+/-2 mmHg, ETPO2 = 130+/-5 mmHg) or isocapnic hypoxia (PETCO2 = 42+/-2, PETO2 + 45+/-2 mmHg) in addition to room air breathing. Measurements by the VIA V-ABG device were compared with paired samples and measurements performed by two ABL Radiometers (505 and 500). Analysis of results includes bias and precision plots and comparison of results with minimal performance criteria as established by CLIA. RESULTS: Nineteen volunteers yielded 222 matched samples. The range of values were 7.32-7.61 for pH, 20.9-51.6 mmHg for PCO2, 27.9-184.5 mmHg for PO2, 134-141 mmol/l for Na, 3.1-4.1 mmol/l for K, and 30.0-50.4% for hematocrit. Bias and precision (+/-2 sd) for pH was 0.01 and 0.04, for PCO2 was 0.4 and 4.8, for PO2 was 1.0 and 17.0, for Na was -0.3 and 5.2, for K was 0.1 and 0.2, and for Hct was 2.0 and 5.4. CONCLUSIONS: Over the range of blood gas values assessed, blood gas measurements by the VIA V-ABG device were clinically acceptable and met minimal performance criteria utilizing current Medicare CLIA proficiency standards. Performance criteria were also met by the VIA V-ABG device for Na, K, and Hct measurements but the range of values was too narrow to allow characterization of clinical acceptability. The VIA V-ABG device appears to perform well compared with the results which have been published for other point-of-care devices. Comparison between different studies investigating point-of-care devices is difficult due to several factors (range of values measured, comparison device, population studied, etc.). Some of these instruments, including the VIA V-ABG device, may serve quite well as point-of-care devices to perform certain tests at the bedside. Whether or not any of these devices can substitute for traditional laboratory blood gas and chemistry measurements remains an issue that is not adequately studied.

Effects of dobutamine, norepinephrine and epinephrine on intramucosal pH and hemodynamics of dogs during endotoxic shock.

This study assessed the effects of dobutamine (DOB), epinephrine (EPI) and norepinephrine (NE) on gastric tissue oxygenation indicated by gastric intramucosal pH (pHi) and hemodynamics in dogs subjected to endotoxic shock. Twenty-four dogs were assigned to four groups of 6 dogs each: endotoxin without catecholamine and endotoxin with DOB, or EPI or NE. Endotoxic shock was induced by intravenous injection of 3 mg/kg of E. coli over 1 min, with an additional 3 mg/kg over the next 2 hrs. Dogs were resuscitated with normal saline to maintain pulmonary capillary wedge pressure (PCWP) near baseline levels. Catecholamines were infused at 0.1, 0.4 and 1.6 micrograms/kg/min (EPI and NE) and 2.5, 5.0 and 10.0 micrograms/kg/min (DOB) for 30 min at each rate. After 2 hrs of endotoxemia, mean arterial pressure (MAP) and cardiac index (CI) and oxygenation delivery index (DO2I) for all dogs decreased by 46.5%, 43.9% and 15.1% respectively, while pHi decreased from 7.47 to 7.10. Endotoxemia increased blood lactate by 142%. Following fluid resuscitation, EPI (1.6 micrograms/kg/min) further increased lactate by 178% (1.22 to 3.4 mmol/L). No correlation was found between tonometry pHi and lactate (R2 = 0.003), pHi and pHa (R2 = 0.231), pHi and DO2I (R2 = 0.056) nor between intramucosal PCO2 and PaCO2 (R2 = 0.005). pHi did not reflect the improvements in cardiovascular hemodynamics observed following administration of catecholamines. NE improved MAP, CI and DO2I whereas DOB produced similar effects as NE but further reduced SVR. EPI produced similar effects as NE. DOB, NE and EPI further decreased pHi. EPI significantly (P < 0.05) increased blood lactate levels more than DOB and NE.

Effects of dobutamine, epinephrine and norepinephrine on the hemodynamics of dogs during hemorrhagic shock.

BACKGROUND: The present study examined how effective epinephrine (EPI), norepinephrine (NOR) and dobutamine (DOB) were for resuscitating dogs subjected to hemorrhagic shock (HS). METHODS: Dogs (n = 42) were randomly assigned to seven test groups: EPI, NOR and DOB infusion with and without HS, and HS dogs with no catecholamine. Following baseline measurements, the dogs were bled to a mean arterial blood pressure of 40 mmHg. After 3 h, the shed blood was reinfused. EPI and NOR (0.1, 0.4 and 1.6 micrograms/kg/min) and DOB (2.5, 5.0 and 10.0 micrograms/kg/min) were given and the dog allowed to stabilize for 30 min. Hemodynamic and blood gas data were obtained at 6 time points (control, shock, resuscitation and after catecholamine infusion). RESULTS: There was no significant difference in myocardial performance (dP/dt) between the respective shocked and unshocked groups after blood resuscitation. In dogs without catecholamine infusion, CO and SvO2 continued to decline whereas SVR increased. DOB (2.5 to 10.0 micrograms/kg/min) with and without shock improved CO, LV dP/dt, SVR and SvO2. EPI did not further improve CO or SvO2 at infusion rates above 0.1 microgram/kg/min (with and without shock). NOR did not improve SvO2 at any infusion rate (with and without shock) and did not improve CO until the infusion rate was at 0.4 microgram/kg/min (without shock). CONCLUSIONS: This study advocates the use of both volume replacement therapy and DOB for resuscitation of HS dogs.

The effect of prior dural puncture on cisternal cerebrospinal fluid morphine concentrations in sheep after administration of lumbar epidural morphine.

Combined spinal epidural anesthesia has become increasingly popular as a method of providing rapid onset of analgesia or surgical block with access for further administration of analgesics or anesthetics. No in vivo studies have evaluated the relationship between dural puncture and drug transfer from the epidural space to the cerebrospinal fluid (CSF). To determine whether morphine administered in the epidural space adjacent to a dural puncture results in increased CSF concentrations at the cisterna magna (CM), 12 adult ewes were studied. Each animal was assigned to one of three groups. Animals in Group 1 served as a control and received no dural puncture. Animals in Group 2 received a dural puncture with a 25-gauge (G) Whitacre needle, while Group 3 animals received a dural puncture with an 18-G Tuohy needle. One hour after dural puncture, each animal was given epidural morphine, 0.2 mg/kg. Six hours after the administration of epidural morphine, CSF from the CM was sampled and analyzed by gas chromatography-mass spectrometry for morphine concentration. The mean morphine concentration at the CM for Group 1 (control) was 22 +/- 12 ng/mL, whereas animals with 25-G and 18-G dural punctures had concentrations of 154 +/- 32 ng/mL and 405 +/- 53 ng/mL, respectively (P = 0.0005). These data demonstrate that a significant increase in CSF morphine concentration at the brainstem will occur when lumbar epidural morphine is administered adjacent to a dural puncture. Furthermore, the increase in CSF morphine concentration is positively correlated with the size of the needle producing the dural puncture. These findings highlight the potential for delayed respiratory depression when epidural opiate administration follows a dural puncture.

Cardiovascular responses to graded doses of three catecholamines during lactic and hydrochloric acidosis in dogs.

We have studied the cardiovascular effects of incremental doses of three catecholamines in dogs subjected to lactic (LAC) and hydrochloric (HCl) acidosis. Fifty-four dogs were allocated randomly to one of three groups: control, LAC and HCl acidosis (n = 18 each group). In the acidotic models, 2 mol litre-1 of lactic acid (4 ml kg-1 h-1) or 2 mol litre-1 of HCl (1 ml kg-1 h-1) was infused i.v. until arterial pH was reduced to 7.00 +/- 0.1. Within each group, six dogs received one of three different drugs in logarithmically incremental doses: adrenaline 0.1, 0.2, 0.4, 0.8, 1.6, 3.2 micrograms kg-1 min-1, noradrenaline 0.1, 0.2, 0.4, 0.8, 1.6, 3.2 micrograms kg-1 min-1 and dobutamine 5, 10, 20, 40, 80, 160 micrograms kg-1 min-1. Cardiovascular variables were monitored, with periodic measurements of plasma electrolyte and lactate concentrations. The pH reduction induced by HCl or lactic acid was associated with a statistically significant increase in mean pulmonary arterial pressure (MPAP), prominent especially in the LAC group where MPAP increased from mean 18 (SD 5) to 27 (6) mm Hg. In the acidotic models, the reduction in myocardial responsiveness to adrenaline or noradrenaline was more prominent than that for the control for corresponding doses of drugs. In the LAC group mean cardiac index decreased significantly from 5.2 (1.8) to 2.2 (0.7) litre min-1 m-2 after infusion of adrenaline 3.2 micrograms kg-1 min-1 and decreased from 5.1 (1.1 to 2.4 (0.9) litre min-1 m-2 after infusion of noradrenaline 3.2 micrograms kg-1 min-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Buccal absorption of fentanyl is pH-dependent in dogs.

BACKGROUND: Analgesia and sedation have been achieved noninvasively by fentanyl administration through the oral and nasal mucosa. In theory, the transmucosal bioavailability and absorption of fentanyl could be improved by converting more fentanyl to the unionized form by adjusting the surrounding pH. The authors tested this hypothesis in dogs. METHODS: Under general anesthesia, each of six mongrel dogs was given fentanyl on repeated occasions, first intravenously (once), then by application to the buccal mucosa (six times). Buccal fentanyl administration was accomplished by placement of a pH-buffered solution of fentanyl into a specially constructed cell, which was clamped to the dog's buccal mucosa for 60 min. Fentanyl solutions with pHs of 6.6, 7.2, and 7.7 were studied to span a tenfold difference in the unionized fraction of fentanyl. Femoral arterial blood samples were sampled frequently and analyzed for fentanyl using a radioimmunoassay. Peak plasma concentration and the time of its occurrence for each buccal study were noted from the plasma concentration verses time profile. Terminal elimination half-life, bioavailability, and permeability coefficients were calculated using standard pharmacokinetic techniques. RESULTS: The variables peak plasma concentration, bioavailability, and permeability coefficient increased three- to fivefold as the pH of the fentanyl buccal solution increased and more fentanyl molecules became unionized. There was no difference in terminal elimination half-life after intravenous fentanyl (244 +/- 68 min) or buccal fentanyl administration (pH 7.7, 205 +/- 89 min; pH 7.2, 205 +/- 65 min; pH 6.6, 196 +/- 48 min). In all buccal studies regardless of pH, time to peak plasma concentration occurred within 10 min of removal of the fentanyl solutions from the buccal mucosa. CONCLUSIONS: The buccal absorption, bioavailability, and permeability of fentanyl are markedly increased as the pH of the fentanyl solution becomes more basic. Most likely, this is because of an increase in the fraction of unionized fentanyl.

Use of gastric intramucosal pH as a monitor during hemorrhagic shock.

During resuscitation of the patient suffering from hemorrhagic shock, it may be difficult to determine the adequacy of treatment in the acute setting. The objective of these preliminary studies was to determine if monitoring perfusion of the gastrointestinal tract as estimated by gastric intramucosal pH (pHi) is useful as a guide during the treatment of hemorrhagic shock. Dogs were bled using a modified Wigger's method to a mean arterial blood pressure of 50 mmHg, and pHi was determined 30, 60, 90, and 120 min later. Gastric intramucosal acidosis developed within 30 min of induction of hemorrhagic shock. It was also found that pHi decreases with relatively small amounts of blood loss. There was a significant fall in pHi following hemorrhage to a mean arterial pressure of 80 mmHg from a baseline pressure of 100 mmHg. Following the reinfusion of shed blood, the pHi returned to baseline values within 30 min. It is concluded that measurements of pHi may be a useful monitor in the evaluation and initial resuscitation of patients in hemorrhagic shock.

A system for automatic feedback control of plasma potassium concentration.

A system is described for automatic feedback control of plasma potassium concentration in experimental animals. Plasma potassium was monitored continuously and the signal compared with the desired plasma potassium concentration. The resulting error signal controlled the infusion rates of a concentrated potassium chloride solution (50 or 200 mmol litre-1) and a solution of 50% glucose with insulin 200 u litre-1. Plasma potassium was increased or decreased to the desired concentration at various rates, dictated by the controller constants. Increases were achieved significantly faster than reductions. The system may prove useful for elucidating the fate of infused potassium and for determining the optimum rate of insulin infusion in hyperkalaemia. If adapted for clinical use, it may find applications in the management of various abnormalities of potassium homeostasis.

Cardiovascular effects of large doses of pentamorphone in the dog.

The cardiovascular effects of large doses of pentamorphone were evaluated in nine mongrel dogs basally anesthetized with sodium thiopental, 25 to 30 mg/kg, intravenously. All dogs were mechanically ventilated with 100% oxygen, and the PaCO2 was maintained between 35 and 40 mm Hg. Mean arterial pressure (MAP), central venous pressure, heart rate (HR), cardiac output (CO), pulmonary artery pressure, and pulmonary artery occluded pressure were measured, and stroke volume and systemic and pulmonary vascular resistances were calculated. Baseline measurements were obtained, then pentamorphone, 10 micrograms/mL, was given as an intravenous infusion at 2.5 micrograms/kg/min. Additional data were obtained after infusion of 25, 50, 75, 100, 125, 150, 200, 250, 300, and 350 micrograms/kg of pentamorphone. The inspired gases were then changed to 50% nitrous oxide in oxygen, and after a 20-minute equilibration period, an additional set of data was collected. Pentamorphone, 25 micrograms/kg, decreased HR 50%, MAP 65%, and CO 54%. No further changes in any measured or calculated variables were observed with additional doses of pentamorphone. The addition of 50% nitrous oxide to the inspired gas mixture had no effect on any measured or calculated hemodynamic variable. The minimal hemodynamic effects of pentamorphone in the dog suggest that further investigation into its use as an anesthetic is warranted.

Preservation of the ischemic canine myocardium: a comparison of hypothermia, lidoflazine, and ketanserin.

The purpose of this study was to determine whether ketanserin protects the globally ischemic canine heart and whether such protection, if present, is independent of that provided by hypothermia or calcium channel blockade with lidoflazine. Forty mongrel dogs, anesthetized with halothane, were divided into eight groups of five and subjected to one hour of global myocardial ischemia during hypothermic (30 degrees C; groups 1 to 4) or normothermic (37 degrees C; groups 5 to 8) cardiopulmonary bypass (CPB). Dogs in groups 1 and 5 served as controls with respect to prebypass myocardial protective therapy, and received only placebo (a normal saline bolus) prior to CPB. Before bypass, dogs in groups 2 and 6 received lidoflazine, 1.25 mg/kg intravenously (IV); those in groups 3 and 7 received ketanserin, 5 mg IV bolus, followed by a continuous infusion at 33 microg/min during bypass. Animals in groups 4 and 8 were given both lidoflazine and ketanserin according to the dosing schedules above. No type of pharmacologic or mechanical cardiovascular support was provided after termination of CPB. Postbypass hemodynamic performance and survival of the unsupported animal were assumed to reflect the degree of myocardial protection during CPB. One minute after bypass, mean arterial pressure and cardiac output were decreased in all groups. Cardiac output was lower in groups 5 to 8 (normothermic CPB) than in groups 1 to 4 (hypothermic CPB). After CPB, left ventricular filling pressures were elevated in all groups kept normothermic and in group 3 (hypothermic CPB plus ketanserin). By 15 minutes after CPB, there were no survivors in groups 5, 7, and 8. Sixty percent of animals in group 6 (normothermic CPB plus lidoflazine) survived to the end of the study. Relative odds of survival were increased 110-fold by hypothermia and sevenfold by lidoflazine. Conversely, treatment with ketanserin was associated with an increased likelihood of nonsurvival. It is concluded that, at the doses studied, ketanserin does not protect the canine myocardium against ischemic injury and may exert a detrimental effect when combined with calcium channel blockade in this setting.

Functional residual capacity as a noninvasive indicator of optimal positive end-expiratory pressure.

We hypothesized that functional residual capacity (FRC) could be used as a noninvasive indicator of "optimal" positive end-expiratory pressure (PEEP), the level of PEEP that results in venous admixture below 15% with an inspired oxygen fraction less than 0.5. We compared several variables for PEEP optimization--oxygen transport, total respiratory system compliance, FRC-based compliance, mixed venous oxygen saturation, end-tidal to arterial carbon dioxide tension difference, and arterial oxygen saturation--by producing four different PEEP levels, 0, 5, 10 and 15 cm H2O, in 24 mongrel dogs in which pulmonary injury was produced. The data were regressed versus PEEP by using analysis of variance for regression. Venous admixture (F1,23 = 149.3; P less than 0.0001), end-tidal to arterial carbon dioxide tension difference (F1,23 = 64.9; P less than 0.0001), and oxygen transport (F1,23 = 95.1; P less than 0.0001) decreased linearly with PEEP. FRC (F1,23 = 248.1; P less than 0.0001) and arterial oxygen saturation (F1,23 = 66.9; P less than 0.0001) increased linearly with PEEP. Total respiratory system compliance (F1,23 = 66.6; P less than 0.0001) and mixed venous oxygen saturation (F1,23 = 12.2; P less than 0.002) had a quadratic relationship with respect to PEEP with a peak at 5 cm H2O. FRC-based compliance did not have a significant relationship to PEEP. The maximum values of total respiratory system compliance, FRC-based compliance, mixed venous oxygen saturation, and oxygen transport did not occur at PEEP levels that corresponded to a venous admixture below 15% ("optimal" PEEP).(ABSTRACT TRUNCATED AT 250 WORDS)

Computer-controlled positive end-expiratory pressure titration for effective oxygenation without frequent blood gases.

We have previously designed a computerized system to automatically deliver PEEP to maintain functional residual capacity (FRC) at a desired value. The purpose of this study was to compare the computerized PEEP titration system with a standard clinical PEEP titration algorithm in the animal adult respiratory distress syndrome (ARDS) model. Thirty mongrel dogs were anesthetized, paralyzed, intubated, and ventilated. An acute pulmonary injury was produced using 0.09 ml/kg of oleic acid. The animals were then given PEEP for 5 h. Arterial and venous blood gases, BP, thermodilution cardiac output, heart rate, body temperature, total respiratory system compliance (Ctr), and end-tidal CO2 were measured every 30 min. FRC was measured using an automated sulfur hexafluoride washout system every 15 min. The animals were allocated randomly to three ten-animal groups. The first group had PEEP titrated using a standard clinical protocol; the remaining two groups had PEEP updated at 15-min intervals under computer control to maintain FRC at 1.4 times the postanesthetized, postparalyzed, preinjury value. The second group received fixed 3-cm H2O PEEP steps. The third group had variable size PEEP steps depending on the output of a proportional, integral, and derivative (PID) controller. PaCO2 was maintained at 35.8 +/- 3.4 (SD) torr. There was a significant difference in PEEP delivered between the three groups (p = .0006) and in FRC (p = .005). There was no significant difference in PaO2 (p = .80) or venous admixture (Qva/Qt) (p = .84) between the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Is fentanyl an anesthetic in the dog?

The authors used the absence of vocalization and movement during application of a hemostat clamped to the first ratchet at the base of the tail as an indication of anesthesia for evaluation of the anesthetic properties of fentanyl in the dog. Eighty-six unpremedicated, unrestrained, untrained mongrel dogs were given one of eight doses of fentanyl citrate (125, 250, 500, 750, 1000, 1500, 2000, and 3000 micrograms/kg) as a single intravenous bolus injection. Dogs breathed spontaneously without oxygen supplementation. Anesthesia was assessed every 5 min until absence of anesthesia was recorded for two consecutive evaluations. Venous plasma samples were obtained in two or three dogs receiving each of the doses of fentanyl 5 min after fentanyl injection and again when application of the tail clamp elicited either vocalization or movement (positive response). Fentanyl resulted in recumbency in all animals except two receiving 125 micrograms/kg. Although all doses of fentanyl produced anesthesia in at least one animal 5 min after injection, the duration of anesthesia was short, responses unpredictable, and anesthesia achieved in all animals only with a dose of 3000 micrograms/kg. Increasing doses of fentanyl resulted in higher plasma fentanyl concentrations 5 min after injection and at the time of the first positive response to tail clamp but there was great variability. All doses of fentanyl caused statistically significant decreases in heart and respiratory rates but none produced apnea or a PaCO2 higher than 67 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)