Intracranial pressure during ketamine administration with spontaneous respiration. An animal experimental model

A sequence of i.v. ketamine injections, 0.5, 2.0, and 5.0 mg/kg body weight, was given to thirty piglets. At the beginning of the investigation, 10 of these animals had a normal intracranial pressure and stable circulation. The intracranial pressure of the remaining 20 piglets was raised to 30 mm Hg, and an additional haemorrhagic shock was induced in 10 of these animals. Those animals with a normal intracranial pressure showed no alteration there of at any of the three doses given, and the arterial pCO2 remained practically unchanged. In contrast, all animals with a raised intracranial pressure, both with and without superimposed haemorrhagic shock, had a significant rise in intracranial pressure and pCO2. These two parameters were found to correlate well with each other. We conclude that in the model used, where the animals were breathing spontaneously, the intracranial pressure rise seen following ketamine application is secondary to the increase in pCO2.     

The effect of ketamine on intracranial pressure during haemorrhagic shock under the conditions of both spontaneous breathing and controlled ventilation

Summary Seventeen piglets of both sexes, seven with O₂/air-buprenorphine anaesthesia and controlled ventilation, and ten unanaesthetized animals with normal, spontaneous respiration, were used for the study. The intracranial pressure of both groups of animals was raised by insufflation of an epidural ballon and the arterial blood pressure was reduced to approximately 70% of the original value by controlled haemorrhage. 0.5 mg/kg body weight of ketamine was given intravenously, followed by a further dose of 2.0 mg/kg body weight of ketamine five minutes later.Both ketamine doses led to a significant rise in the intracranial pressure of those animals breathing spontaneously (31.8 mm Hg to 39.1 mm Hg). In contrast, the ventilated animals showed a significant reduction in intracranial pressure. No changes in arterial PCO₂ were observed in this group, while those piglets breathing spontaneously had dangerous PCO₂ rises. At both ketamine doses a significant correlation could be found between the PCO₂ and the intracranial pressure.     

Comparison of halothane, isoflurane, alfentanil, and ketamine in experimental septic shock

The effects of four commonly used anesthetic agents, halothane, isoflurane, alfentanil, and ketamine, on cardiovascular function and oxygen balance were studied in a dog model of septic shock. After initial pentobarbital administration, the dogs were given Escherichia coli endotoxin (3 mg/kg) and, after 30 min, fluids to restore cardiac filling pressures to baseline levels. This resulted in a low resistance shock in all animals. Dogs were then given for 2 h either halothane (n = 9, 0.5 MAC), isoflurane (n = 9, 0.5 MAC), or alfentanil (n = 9, 150 micrograms/kg IV plus 2 micrograms.kg-1.min-1) or ketamine (n = 9, 2 mg/kg IV plus 0.2 mg.kg-1.min-1) or no anesthetic (control: n = 9). Mean arterial pressure increased in the control group (+11 +/- 18 mm Hg) and with ketamine (+10 +/- 20 mm Hg), remained unchanged with isoflurane (-2 +/- 11 mm Hg), and decreased with halothane (-22 +/- 23 mm Hg) and alfentanil (-9 +/- 23 mm Hg). Heart rate tended to increase in the control group but decreased with the four anesthetic agents, especially with alfentanil and halothane. Cardiac index and left ventricular stroke work index increased in the control group and in each anesthetic group except the halothane group. Systemic vascular resistance decreased in all groups except in the ketamine group. In the control group, the increase in cardiac index was associated with significant increases in oxygen delivery and consumption, and with a significant decrease in blood lactate levels. There was a dramatic decrease in oxygen consumption in all anesthetic groups, whereas oxygen delivery failed to increase only with halothane. Blood lactate increased significantly with halothane (5.0 +/- 1.5 to 6.3 +/- 1.4 mM/L) and isoflurane (4.8 +/- 1.1 to 5.3 +/- 1.2 mM/L), remained unchanged with alfentanil (4.5 +/- 1.5 and 4.6 +/- 0.8 mM/L), and tended to decrease with ketamine (4.9 +/- 1.4 to 4.5 +/- 1.4 mM/L). In conclusion, among the four anesthetic agents tested, halothane had the least desirable effects. Ketamine best preserved cardiovascular function and appeared to have the least deleterious effects on the hypoxic tissues. Thus, ketamine could be the anesthetic agent of choice in septic shock.     

L-arginine and nitroglycerin restore hypercapnia-induced cerebral vasodilation in rabbits after its attenuation by ketamine

Although it has been reported that ketamine attenuates hypercapnia-induced cerebral vasodilation, the mechanism remains unknown. Because nitric oxide is involved in cerebral CO2 reactivity, we studied the effects of L-arginine and nitroglycerin on ketamine-mediated attenuation of vascular responses to hypercapnia. Under pentobarbital anesthesia, 16 rabbits underwent closed cranial window preparation. Hypercapnic challenges were repeated after IV saline, ketamine (10 mg/kg, followed by 20 mg x kg(-1) x h(-1)), or ketamine plus either L-arginine (150 mg/kg, followed by 100 mg x kg(-1) x h(-1); n = 8) or nitroglycerin (5 microg x kg(-1) x min(-1) infusion; n = 8). Ketamine reduced hypercapnia-induced cerebral vasodilation (1.27%/mm Hg +/- 0.45%/mm Hg [saline] versus 0.82%/mm Hg +/- 0.53%/mm Hg [ketamine]: P < 0.05), but L-arginine restored reactivity (1.28%/mm Hg +/- 0.73%/mm Hg: P < 0.05 versus ketamine), as did nitroglycerin (1.14%/mm Hg +/- 0.73%/mm Hg [saline] versus 0.56%/mm Hg +/- 0.63%/mm Hg [ketamine]: P < 0.05, and 1.15%/mm Hg +/- 0.74%/mm Hg [ketamine plus nitroglycerin]: P < 0.05 versus ketamine). This indicates that ketamine attenuates cerebral CO2 reactivity, at least in part, via suppression of nitric oxide-cyclic guanosine monophosphate mechanisms in the cerebral vasculature. IMPLICATIONS: The attenuation of cerebral vasodilation to hypercapnia seen under ketamine anesthesia is reversed by L-arginine or nitroglycerin infusion.     

Cerebral blood volume and CSF pressure following administration of ketamine in dogs; modification by pre- or posttreatment with hypocapnia or diazepam

The effects of ketamine (2 mg/kg) on cerebral blood (CBV) and cerebrospinal fluid (CSF) pressure, and the modification of ketamine's effects by pre- or posttreatment with hypocapnia (PaCO2 of 20-25 mm Hg) or diazepam (0.3 mg/kg) were determined in 26 dogs. In Group I (n = 7), the sequence of experimental treatments was as follows: control, ketamine, hypocapnia, and normocapnia. In Group II (n = 7), the sequence was control, hypocapnia, ketamine, and normocapnia. In Group III (n = 6), the sequence was control, ketamine, and diazepam. In Group IV In (n = 6), the sequence was control, diazepam, and ketamine. Ketamine alone increased CBV by 11.7 +/- 6.6 (Group III) to 12.4 +/- 6.9% (Group I) (mean +/- SD) and increased CSF pressure by 6.0 +/- 3.9 (Group I) to 10.7 +/- 5.2 (Group III) cm H2O. Pretreatment with hypocapnia or diazepam reduced CSF pressure and CBV so that when ketamine was administered after 15 min of hypocapnia or diazepam, CSF pressure and CBV rose only to prehypocapnia or prediazepam levels. When hypocapnia or diazepam were administered 15 min after ketamine, CSF pressure and CBV decreased to preketamine levels. For all treatments, CSF pressure changed in parallel with CBV in the absence of significant changes in PaCO2, expired CO2, or mean arterial blood pressure (except for a decrease of mean arterial blood pressure with diazepam pretreatment). We conclude the following: (a) ketamine increases CBV concomitant with increases in CSF pressure, (b) ketamine increases CBV and CSF pressure independent of significant change in PaCO2, and (c) pre- or posttreatment with hypocapnia or diazepam reverses ketamine-induced increase of CBV and CSF pressure in dogs with normal CSF pressure and no cerebrovascular damage.     

Influence of Ketamine on Non-Pregnant Uterus in Vivo

This investigation was performed to evaluate the effect of ketamine anesthesia on non-pregnant uterine activity. Seven healthy non-pregnant women took part in the study. Anesthesia was induced with an i.v. bolus injection of ketamine 2 mg/kg and maintained with a continuous i.v. ketamine infusion, mean dosage 39 μg/kg/min. Before induction of anesthesia, each patient was placed in the lithotomy position, and a catheter fitted with two microtransducers for monitoring of intra-uterine pressures was fed through the cervix into the uterine cavity. For determination of plasma concentrations of ketamine and norketamine, venous blood samples were collected. The assay was based on a gas-liquid chromatographic technique. It was found that ketamine induced an increased uterine activity, both in basal tone and intensity of contractions. Only minor effects on the frequency were observed. This stimulatory effect was simultaneous with a hemodynamic stimulation with increases in heart rate and arterial blood pressure, and with the peak plasma concentration of ketamine.     

Induction dose-response curves for midazolam and ketamine in premedicated ASA class III and IV patients

Using probit analysis, dose-response curves for induction of anesthesia with midazolam or ketamine were constructed in ASA class III and IV patients premedicated with morphine, 0.1 mg/kg, and glycopyrrolate, 4 micrograms/kg. For ketamine, ED50 values for abolition of the response to verbal commands, eyelash stimulation, and painful stimulation were 0.9, 1.3, and 1.3 mg/kg, respectively; corresponding ED95 values were 1.6, 2.3, and 4.3 mg/kg, which are within the range of clinically recommended doses. For midazolam, ED50 values for verbal commands, eyelash stimulation, and painful stimulation were 0.19, 0.24, and 0.36 mg/kg, significantly greater than those previously reported for unpremedicated ASA class I and II patients. The corresponding ED95 values, 0.35, 0.43, and 1.04 mg/kg exceed previously reported values and are appreciably greater than the doses used in most previous studies of midazolam induction. Midazolam decreased systolic blood pressure slightly but significantly (from 138 +/- 4 to 128 +/- 4 mm Hg, mean +/- SEM, P less than 0.005), while diastolic blood pressure and heart rate remained unchanged. In contrast, ketamine increased systolic blood pressure (from 141 +/- 4 to 164 +/- 5 mm Hg, P less than 0.005), diastolic blood pressure (from 71 +/- 3 to 88 +/- 4 mm Hg, P less than 0.005), and heart rate (from 84 +/- 2 to 102 +/- 4 beats/min, P less than 0.005). On the basis of these data, we conclude that in ASA class III and IV patients, midazolam induction allows for hemodynamic stability and avoids the significant tachycardia and hypertension associated with equipotent doses of ketamine.     

Hepatic energy metabolism during ketamine and isoflurane anaesthesia in haemorrhagic shock

The effects of ketamine and isoflurane on the phosphoenergetic state of the liver during haemorrhage were investigated using 31P nuclear magnetic resonance (NMR) spectroscopy. Male Wistar rats were anaesthetized with ketamine (1.0 mg kg-1 min-1 i.v., Ket 1.0 group, or 1.5 mg kg-1 min-1 i.v., Ket 1.5 group), or isoflurane 1.4% (Iso group). Haemorrhage was induced by withdrawing blood until the mean arterial pressure was reduced to 40 mm Hg, and this pressure level was then maintained for 45 min. Hepatic energy metabolism was evaluated from the changes in adenosine triphosphate (ATP) and inorganic phosphate (Pi). The beta-ATP decrease and the Pi increase were more marked in the two Ket groups than in the Iso group. At 20 min after haemorrhage, the beta- ATP peak areas were 34%, 32% and 76%, and the Pi peak areas were 257%, 260% and 160% of their initial values in the Ket 1.0, Ket 1.5 and Iso groups, respectively. NMR data were supported by chemical assessments. These results demonstrated that, in terms of phosphoenergetic levels, a continuous administration of 1.0 or 1.5 mg kg-1 min-1 ketamine markedly decreased hepatic metabolism during haemorrhagic shock, whereas inhalation of 1.4% isoflurane mitigates the metabolic damage.      

Glomerular hemodynamics in mercury-induced acute renal failure

As manifest by tubular collapse and the virtual absence of flow into the glomerulotubular junction (GTJ), filtration in most nephrons (SNGFR) of rats poisoned with 9 mg/kg body wt HgCl2 16 to 28 hours earlier was virtually absent. Arterial colloid osmotic pressure (COPA) and Bowman's space pressure (PBS) were modestly depressed (P less than 0.05 or below), and mean blood pressure was reduced from 115 +/- 2 mm Hg (SEM) to 97 +/- 1 mm Hg (P less than 0.001). Glomerular capillary hydraulic pressure (Pg), 25.6 +/- 1.3 mm Hg was some 24 mm Hg lower than control (P less than 0.001) and yielded a net afferent effective filtration pressure (Pnet) of 4.1 +/- 1.2 mm Hg. Excluding three rats with values greater than 10 mm Hg, Pnet averaged 2.0 +/- 0.9 mm Hg (N = 17 rats) versus 20.0 +/- 1.8 mm Hg in controls (N = 10, P less than 0.001), the former being statistically almost indistinguishable from 0 mm Hg and barely able to support any filtration. This decrease in Pg was caused by a major increase in preglomerular resistance (RA) and a reciprocal fall in efferent arteriolar resistance (RE), the RA/RE ratio of 7.2 +/- 0.8 being fourfold higher than control (P less than 0.001). Renocortical blood flow was not different from control (P greater than 0.2). A wide spread of Pg values in individual glomeruli and the absence of tubular flow despite the appearance of i.v. injected lissamine green in a quadrant of surface glomeruli suggested the possibility of a greatly increased, glomerular capillary resistance. It is concluded that reciprocal changes in RA and RE are the immediate cause of filtration failure in this form of ARF and that, in the virtual absence of filtration, tubular leakage can play no important role. Since PBS was depressed in both the developmental and established phases of ARF, tubular obstruction appears to play no direct role in the pathogenesis of this particular model of murine acute renal failure.     

Propofol vs. thiopental-isoflurane for neurosurgical anesthesia: comparison of hemodynamics, CSF pressure, and recovery

Sixty otherwise healthy patients with no clinical signs of intracranial hypertension who were undergoing elective intracranial surgery were randomly assigned to receive anesthesia with either thiopental, 3-6 mg/kg i.v., and isoflurane, 0.5-1.5% (group 1, N = 30) or propofol, 1-2.5 mg/kg i.v., and propofol infusion, 40-200 microg/kg/h (group 2, N = 30). Both groups received 50% nitrous oxide in O2 subsequent to dural opening. During induction, the changes in heart rate (HR), mean arterial pressure (MAP), cerebrospinal fluid pressure (CSFP), and cerebral perfusion pressure (CPP) were similar between the groups, except at 3 min when the findings (mean +/- SEM) for CPP (81 +/- 3.3 vs. 70.3 +/- 2.8 mm Hg, p <0.05) were significantly lower in group 2. At intubation, the highest level of MAP (103.1 +/- 3.3 vs. 88.9 +/- 2.7 mm Hg, p <0.05) was significantly greater in group 1. At pinhead-holder application, the highest values of HR (81.8 +/- 3 vs. 73.9 +/- 2.1 beats/min, p <0.05), MAP (112.2 +/- 3.6 vs. 98.3 +/- 3 mm Hg, p <0.05), CSFP (15.2 +/- 1.3 vs. 11.6 +/- 1.1 mm Hg, p <0.05), and CPP (97.0 +/- 3.9 vs. 86.7 +/- 3.3 mm Hg, p <0.05) were significantly greater in group 1. During early (20-30 min) recovery, group 2 had higher Glasgow Coma Scale scores and a greater percentage of patients in whom eye opening, response to commands, extubation, speech, and time/space orientation were present. In conclusion, when compared to thiopentalisoflurane for intracranial surgery, propofol produces similar HR, MAP, CSFP, and CPP responses during induction, adequate control of these responses during nociceptive stimulation, and faster recovery for cerebral function postoperatively.     

The influence of ketamine on both normal and raised intracranial pressure of artificially ventilated animals

The effect of two different doses of ketamine, 0.5 mg kg-1 body weight, and 2.0 mg kg-1 body weight, on intracranial pressure and cerebral perfusion pressure were investigated in 21 young pigs (26-34 kg) under controlled artificial ventilation. Three groups each containing seven animals were studied: Group 1. Initially normal blood pressure and an intracranial pressure within the normal range (10.7 mmHg). Group 2. Normal blood pressure and increased intracranial pressure caused by inflating an epidural balloon (29.2 mmHg). Group 3. Increased intracranial pressure (32.7 mmHg) and mean arterial pressure reduced by approximately 30% through controlled haemorrhage. There was no increase in intracranial pressure from either normal or initially increased values. This applied to animals with normal blood pressure values and also to those in haemorrhagic shock. This observation can be explained by the lack of an increase in PCO2 under controlled ventilation. During haemorrhagic shock cerebral perfusion pressure fell significantly as a result of the fall in mean arterial pressure. This particularly applied to the 2.0 mg kg-1 dose of ketamine. We therefore consider volume substitution to be essential in this situation.     

Midazolam and ketamine for rectal premedication and induction of anesthesia in children

Fifteen healthy children 2-10 years old and scheduled for elective surgery, received midazolam 0.35 mg/kg body weight and atropine 0.025 mg/kg as rectal premedication about 35 min before the induction of anesthesia. The induction itself was carried out in a separate and quiet room next to the operating theatre by rectal administration of ketamine 10 mg/kg and midazolam 0.2 mg/kg. With the children breathing spontaneously, anesthesia was maintained by repetitive i.v. bolus injections of ketamine. The sedative and anticholinergic effects of the premedication were satisfactory. Induction of anesthesia was smooth. Consciousness was lost after 9-15 (mean 13) min. No significant adverse effects on hemodynamics or respiration were noted. Recovery from anesthesia was uneventful. No cases of rectal irritation or unpleasant dreams were reported. Post-operative analgesia was good. In conclusion, rectal administration of midazolam and atropine for premedication, followed by ketamine and midazolam for the induction of anesthesia, proved to be a pleasant, safe, and reliable method in pediatric anesthesia.     

Effects of ethanol on spinal cord blood flow in the rat

This study examines the effects of low and high concentrations of ethanol on spinal cord blood flow (SCBF) in the rat. SCBF was measured in the following blood pressure ranges: (a) <60 mm Hg, (b) 60-90 mm Hg, (c) 90-120 mm Hg, (d) 120-150 mm Hg, and (e) >150 mm Hg. Rats were anesthetized with 1.4% isoflurane in air and randomly assigned to the following treatment groups: group 1 (n = 12), intraperitoneal (i.p.) saline injection; group 2 (n = 10), 1 g/kg of ethanol i.p.; and group 3 (n = 14), 4 g/kg of ethanol i.p. Blood pressure was increased by intravenous phenylephrine infusion or lowered by a combination of intravenous trimethaphan and blood withdrawal. The SCBF was measured in cervical, thoracic, and lumbar segments using radioactive microspheres. The plasma ethanol concentration was 0 mg/ml for group 1, 0.64 +/- 0.06 mg/ml (mean +/- SEM) in group 2, and 4.18 +/- 0.11 mg/ml in group 3. In control rats, the cervical SCBF was higher than the thoracic or lumbar SCBF, evaluated over the entire blood pressure range (analysis of variance, p <0.05). This difference in regional SCBF was abolished by ethanol. Ethanol produced a significant decrease in cervical and lumbar SCBF (p <0.05) but not thoracic SCBF (p = 0.07). This decrease in SCBF was most pronounced at high blood pressures. These results suggest that ethanol produces vasoconstriction in the spinal cord that is countered by autoregulatory vasodilation at low blood pressures.     

Plasma Free Norepinephrine and Epinephrine Concentrations Following Diazepam-Ketamine Induction in Patients Undergoing Cardiac Surgery

Ketamine causes cardiovascular stimulation, presumably, by increasing central sympathetic activity. This study was undertaken to find out if diazepam in appropriate doses could abolish or moderate the central sympathetic and cardiovascular stimulation following ketamine in patients undergoing cardiac surgery. Twelve patients, scheduled for valvular replacement (8) and direct aortocoronary bypass graft operations (4) were studied. After premedication with diazepam 0.15 mg/kg orally and morphine sulphate 0.15 mg/kg i.m., they were induced with diazepam 0.3 mg/kg i.v., followed 10 min later by ketamine 2 mg/kg i.v. Direct arterial pressure by a strain gauge from the radial artery and heart rate by EKG were continuously recorded. Plasma free norepinephrine, measured by Vendsalu's method, in the arterial blood was 0.39 +/- 0.03 ng/ml prior to induction, 0.39 +/- 0.03 ng/ml 10 min after diazepam and 0.42 +/- 0.05 ng/ml (P greater than 0.05) 5 min after ketamine administration. Plasma free epinephrine concentrations were 0.10 +/- 0.04 ng/ml prior to induction, 0.06 +/- 0.03 ng/ml (P less than 0.05) 10 min after diazepam and 0.01 +/- 0.003 ng/ml (P less than 0.05) 5 min after ketamine. Heart rate and systolic pressure did not change significantly throughout the study period. Diastolic pressures were elevated significantly (P less than 0.05) 5 min after ketamine administration, amounting to a 12% increase over baseline. Diazepam-ketamine induction in cardiac surgical patients did not result in clinically significant central sympathetic or cardiovascular stimulation.     

Antagonism of the cardiovascular effects of ketamine by diazepam in volunteers

In healthy volunteers pretreated with atropine (0.5 mg), ketamine given as a bolus i.v. injection (2 mg/kg) followed by an infusion of ketamine (1 mg/kg/hr) for one hour, caused a significant rise in blood pressure and heart rate. This cardiovascular stimulation was rapidly counteracted by diazepam (0.2 mg/kg i.v.) given when the response to ketamine was already maximal.     

Comparison of femoral and carotid blood pressure during laparoscopy in piglets

PurposeThe impact of a capnoperitoneum on the known blood pressure (BP) difference of the upper and lower limb was studied in piglets.MethodsEleven German Landrace piglets (body weight, 4.3-7.4 kg; mean body weight, 6.2 kg) were studied. Arterial lines were placed in the right carotid and right femoral artery for pressure monitoring. Intraabdominal pressure levels were increased in steps of 6 mm Hg up to 24 mm Hg.ResultsWe found that elevated intraabdominal pressures up to 24 mm Hg did not change the preexisting systolic BP difference between the carotid and femoral arteries. Systolic femoral artery pressure constantly remained 5% higher than its carotid counterpart. In addition, mean and diastolic values were not affected.ConclusionsArterial BP measurements recorded at the legs of piglets when abdominal pressure is increased by up to 24 mm Hg can be used for intraoperative assessment of systemic arterial BP.     

Intraartikuläre Ketamingabe bei arthroskopischen Knieoperationen

BACKGROUND: Surgery of the knee can be very painful and sufficient postoperative pain treatment is often problematic. To optimize postoperative analgesia, application of local analgesics has been suggested. In the present study it was investigated whether intra-articular administration of ketamine reduces the level of pain after arthroscopic knee surgery. MATERIAL AND METHODS: A total of 68 patients undergoing arthroscopic knee surgery were randomized into 4 groups. At the end of surgery the following pharmaceuticals were administered: 10 ml 0.25% bupivacaine intra-articular (i.a.), 0.25 mg S-(+)-ketamine/kg body weight to 10 ml in 0.9% NaCl i.a., 0.25 mg S-(+)-ketamine/kg body weight intravenous (i.v.), and 10 ml 0.9% NaCl i.a. as placebo. Postoperative pain therapy was performed as i.v. patient controlled analgesia (PCA) with piritramide. Postoperative opioid consumption and pain intensity were assessed as the main criteria in the postoperative course. RESULTS: All 4 groups were comparable with respect to biometrical data. The scores of the visual analogue scale (VAS) showed a significantly (p<0.05) lower pain intensity in patients treated with ketamine i.a. or i.v. compared to the other groups. Shortly after surgery the highest reduction of pain was detected in the i.a. ketamine group compared to i.a. bupivacaine or placebo administration. The postoperative opioid consumption was always lowest in the i.a. ketamine group. A significant difference in piritramide consumption (p<0.05) was demonstrated in the first 20 min after operation in the i.a. ketamine group compared to the i.a. administration of placebo and bupivacaine. CONCLUSIONS: The i.a. application of ketamine after arthroscopic knee surgery leads to a significant decrease of postoperative analgesic demand and decreases patients' subjective level of pain compared to i.a. application of bupivacaine or placebo. Likewise, the i.v. application of ketamine is similarly effective but the effect is of shorter duration.     

Racemic ketamine does not abolish cerebrovascular autoregulation in the pig

BACKGROUND: Little is known about the influence of racemic ketamine on autoregulation of cerebral blood flow (CBF), and available reports regarding its influence on cerebral hemodynamics are contradictory. This study was designed to evaluate cerebrovascular responses to changes in the mean arterial pressure (MAP) during ketamine anesthesia. METHODS: In eight normoventilated pigs anesthesia was induced with propofol and maintained by i.v. infusion of ketamine (15.0 mg kg(-1) x h(-1)) during measurements. The intra-arterial xenon clearance technique was used to calculate CBF. Balloon-tipped catheters were introduced in the inferior caval vein and mid-aorta, and increases or decreases by up to 40% in mean arterial pressure (MAP) in random order were achieved by titrated inflation of these balloon catheters. Cerebral blood flow was determined at each MAP level. Regression coefficients of linear pressure-flow curves were calculated in all animals. RESULTS: From the mean baseline level (101 mmHg) MAP was reduced by 20% and 40%, and increased by 26% and 43%. The maximal mean increase and decrease in MAP induced a 12% increase and a 15% decrease, respectively, of CBF from the mean baseline level (52.6 ml.100 g(-1) x min1). The 95% confidence interval (-0.02; 0.38) of the mean regression coefficient of individual pressure-flow curves does not include the regression coefficient (0.64) of a linear correlation between MAP and CBF including origo (correlation coefficient 0.99), which indicates complete lack of cerebrovascular autoregulation. CONCLUSIONS: We conclude that autoregulation of CBF is not abolished during continuous ketamine infusion in normoventilated pigs and that previous divergent conclusions are unlikely to be associated with severe impairment of cerebrovascular autoregulation.     

Relationship between volume status and blood pressure during chronic hemodialysis.

BACKGROUND: The relationship between volume status and blood pressure (BP) in chronic hemodialysis (HD) patients remains incompletely understood. Specifically, the effect of interdialytic fluid accumulation (or intradialytic fluid removal) on BP is controversial. METHODS: We determined the association of the intradialytic decrease in body weight (as an indicator of interdialytic fluid gain) and the intradialytic decrease in plasma volume (as an indicator of postdialysis volume status) with predialysis and postdialysis BP in a cross-sectional analysis of a subset of patients (N=468) from the Hemodialysis (HEMO) Study. Fifty-five percent of patients were female, 62% were black, 43% were diabetic and 72% were prescribed antihypertensive medications. Dry weight was defined as the postdialysis body weight below which the patient developed symptomatic hypotension or muscle cramps in the absence of edema. The intradialytic decrease in plasma volume was calculated from predialysis and postdialysis total plasma protein concentrations and was expressed as a percentage of the plasma volume at the beginning of HD. RESULTS: Predialysis systolic and diastolic BP values were 153.1 +/- 24.7 (mean +/- SD) and 81.7 +/- 14.8 mm Hg, respectively; postdialysis systolic and diastolic BP values were 136.6 +/- 22.7 and 73.9 +/- 13.6 mm Hg, respectively. As a result of HD, body weight was reduced by 3.1 +/- 1.3 kg and plasma volume was contracted by 10.1 +/- 9.5%. Multiple linear regression analyses showed that each kg reduction in body weight during HD was associated with a 2.95 mm Hg (P=0.004) and a 1.65 mm Hg (P=NS) higher predialysis and postdialysis systolic BP, respectively. In contrast, each 5% greater contraction of plasma volume during HD was associated with a 1.50 mm Hg (P=0.026) and a 2.56 mm Hg (P < 0.001) lower predialysis and postdialysis systolic BP, respectively. The effects of intradialytic decreases in body weight and plasma volume were greater on systolic BP than on diastolic BP. CONCLUSIONS: HD treatment generally reduces BP, and these reductions in BP are associated with intradialytic decreases in both body weight and plasma volume. The absolute predialysis and postdialysis BP levels are influenced differently by acute intradialytic decreases in body weight and acute intradialytic decreases in plasma volume; these parameters provide different information regarding volume status and may be dissociated from each other. Therefore, evaluation of volume status in chronic HD patients requires, at minimum, assessments of both interdialytic fluid accumulation (or the intradialytic decrease in body weight) and postdialysis volume overload.     

CARDIOVASCULAR EFFECTS OF PANCURONIUM IN MAN

We have investigated the effects of pancuronium bromide (0.07mg/kg body weight) on heart rate, mean arterial blood pressure,cardiac output and calculated total peripheral resistance inten artificially ventilated patients, anaesthetized with 60per cent nitrous oxide in oxygen plus phenoperidine (1 mg/15kg body weight). End-tidal Pco₂ was maintained constant at 30±2mm Hg. There was a marked and statistically significant increaseof heart rate of about 25 per cent, accompanied by lesser, butstill statistically significant, incerases of cardiac outputand mean arterial blood pressure. Total peripheral resistancewas unchanged, suggesting that pancuronium has little ganglion-blockingactivity.