Effects of cisatracurium on cerebral and cardiovascular hemodynamics in patients with severe brain injury

BACKGROUND: For neuroanesthesia and neurocritical care the use of drugs that do not increase or preferentially decrease intracranial pressure (ICP) or change cerebral perfusion pressure (CPP) and cerebral blood flow (CBF) are preferred. The current study investigates the effects of a single rapid bolus dose of cisatracurium on cerebral blood flow velocity, ICP, CPP, mean arterial pressure (MAP) and heart rate (HR) in 24 mechanically ventilated patients with intracranial hypertension after severe brain trauma (Glasgow coma scale <6) under continuous sedation with sufentanil and midazolam. METHODS: Patients were randomly assigned to receive either 2xED95 (n=12) or 4xED95 (n=12) of cisatracurium as a rapid i.v. bolus injection. Before and after bolus administration mean cerebral blood flow velocity (BFV, cm/s) was measured in the middle cerebral artery using a 2-MHz transcranial Doppler sonography system, ICP (mm Hg) was measured using an extradural probe, and MAP (mm Hg) and HR (b/min) were measured during a study period of 20 min. Cerebral perfusion pressure (CPP=MAP-ICP) was also calculated. RESULTS: Our data show that a single bolus dose of up to 4xED95 cisatracurium caused no significant (P<0.05) changes in BFV, ICP, CPP, MAP and HR. Possible histamine-related events were not observed during the study. CONCLUSIONS: The results from this study suggest that cisatracurium is a safe neuromuscular blocking agent for use in adult severe brain-injured patients with increased ICP under mild hyperventilation and continuous sedation.     

Intravascular ultrasound in endovascular stent-grafts for peripheral aneurysm: a clinical study

The present series of experiments was performed to investigate the influence of acute intracranial hypertension on the upper limit (UL) of cerebral blood flow (CBF) autoregulation. Three groups of eight rats each--one with normal intracranial pressure (ICP) (2 mmHg), one with ICP = 30 mmHg, and one with ICP = 50 mmHg--were investigated. Intracranial hypertension was maintained by continuous infusion of lactated Ringer's solution into the cisterna magna, where the pressure was used as ICP. Cerebral perfusion pressure (CPP), calculated as mean arterial blood pressure (MABP)-ICP, was increased stepwise by continuous intravenous infusion of norepinephrine. CBF was calculated by the intracarotid 133Xe method. In all three groups the corresponding CBF/CPP curve included a plateau where CBF was independent of changes in CPP, showing intact autoregulation. At normal ICP the UL was found at a CPP of 141 +/-2 mmHg, at ICP = 30 mmHg the UL was 103+/-5 mmHg, and at ICP = 50 mmHg the UL was found at 88+/-7 mmHg. This shift of the UL was more pronounced than the shift of the lower limit (LL) of the CBF autoregulation found previously. We conclude that intracranial hypertension is followed by both a shift toward lower CPP values and a narrowing of the autoregulated interval between the LL and the UL.     

Opioids, cerebral circulation and intracranial pressure

The effects of the opioids alfentanil (A), fentanyl (F), and sufentanil (S) on cerebral blood flow (CBF) and intracranial pressure (ICP) have been discussed in several recent publications. The purpose of this review is to describe the results of studies in animals, healthy volunteers, and patients with and without intracranial diseases. Clinical relevance and mechanisms of the reported ICP and CBF increases are analysed. METHODS. Approximately 70 original articles and abstracts were retrieved by a systematic literature search using the key word list at the end of this abstract. The cited studies came from computerised database systems like Silver Platter and DIMDI, the SNACC reference list, and the bibliographies of pertinent articles and books. These studies were classified into three groups: significant increase of ICP and/or CBF; no significant or clinically relevant alterations; and significant decreases of ICP and/or CBF. RESULTS. The numerical relationship was 6:7:3 for A, 7:16:9 for F, and 5:11:8 for S. Increases of previously normal or only slightly elevated ICP were registered in some studies in connection with a decrease in mean arterial pressure (MAP). On the other hand, in patients with brain injury and elevated ICP opioids did not further increase ICP despite MAP decreases. In studies monitoring ICP and/or CBF continuously, transient and moderate increases of questionable clinical relevance became apparent a few minutes after bolus injection of opioids. Alterations of systemic and cerebral haemodynamics observed after bolus application were not registered during continuous infusion of A and S. DISCUSSION AND CONCLUSIONS. The cerebral effects of opioids are dependent on several factors, e.g., age, species, ventilation, anaesthesia before and during measurements, systemic haemodynamics, and underlying diseases. The probable mechanism of ICP increase during decreasing MAP is cerebral vasodilatation due to maintained autoregulation. With increasing severity of the cerebral lesion autoregulation is often disturbed. Therefore, ICP often remains unaltered despite MAP decreases. However, the resulting decrease in cerebral perfusion pressure makes such patients more susceptible to develop ischaemic neurological deficits. Induction of somatic rigidity or (with high doses) convulsions, exceeding the upper limit of autoregulation, histamine release, cerebral vasodilatation, increased cerebral oxygen consumption, or carbon dioxide accumulation during spontaneous breathing were discussed as mechanisms for transient ICP/CBF increases. It is concluded that opioids are often beneficial and not generally contraindicated for patients with cerebral diseases and compromised intracranial compliance. However, since negative side effects cannot be excluded, opioid effects and side effects should be monitored (MAP, ICP, cerebrovenous oxygen saturation, transcranial Doppler sonography) in patients at risk. It has to be stressed that opioids should be administered only to patients with stable haemodynamic situations and preferably in well-titrated, continuous infusions.     

Inhibition of nitric oxide synthesis extends cerebrovascular autoregulation during hypertension

In anesthetized intact rats, cerebral blood flow is autoregulated until mean arterial blood pressure (MAP) exceeds 150 mmHg. At higher pressures cerebral blood flow breaks through autoregulation and rapidly increases. However, interruption of the arterial baroreceptor reflex eliminates breakthrough of autoregulation. Thus, breakthrough may reflect active rather than passive vasodilatation. We, therefore, sought to determine if breakthrough depends upon synthesis of the vasodilator nitric oxide. Thirty-eight anesthetized adult male Sprague-Dawley rats were studied. In all, MAP was raised by slow i.v. infusion of phenylephrine. In rats pretreated with the nitric oxide synthase inhibitor L-nitroarginine (L-NA; 22 mg/kg i.v.) or with a combination of L-NA plus D-arginine (D-Arg; 240 mg/kg i.v.), breakthrough did not occur even when MAP exceeded 185 mmHg (L-NA) and 165 mmHg (D-Arg). In contrast, breakthrough occurred in rats treated with L-NA plus L-arginine (L-Arg; 240 mg/kg i.v.) and in rats whose basal vascular tone had been increased by pretreatment with arginine vasopressin prior to infusion of phenylephrine. Removal of sympathetic innervation to cerebral vessels attenuated, but did not eliminate, effects of L-NA on breakthrough. Thus, vasodilatation seen with breakthrough of autoregulation depends upon release of nitric oxide or a nitric oxide donor.     

The effect of clonidine on cerebral blood flow velocity, carbon dioxide cerebral vasoreactivity, and response to increased arterial pressure in human volunteers

BACKGROUND: Because patients may be taking clonidine chronically or may be receiving it as a premedication before surgery, the authors investigated its effect on cerebral hemodynamics. METHODS: In nine volunteers, middle cerebral artery mean blood flow velocity (Vm) was measured using transcranial Doppler ultrasonography (TCD). CO2 vasoreactivity was measured before clonidine administration (preclonidine), 90 min after clonidine, 5 microg/kg orally, then following restoration of mean arterial pressure (MAP) to the preclonidine level. In addition, Vm was measured after a phenylephrine-induced 30-mmHg increase in MAP. RESULTS: After clonidine administration, Vm decreased from 62 +/- 9 to 48 +/- 8 cm/s (P < 0.01), and MAP decreased from 86 +/- 10 to 63 +/- 5 mmHg (P < 0.01; mean +/- SD). Clonidine decreased the CO2 vasoreactivity slope from 2.2 +/- 0.4 to 1.2 +/- 0.5 cm x s(-1) x mmHg(-1) (P < 0.05); restoring MAP to the preclonidine level increased the slope to 1.60 +/- 0.5 cm x s(-1) x mmHg(-1), still less than the preclonidine slope (P < 0.05). CO2 vasoreactivity expressed as a percentage change in Vm, decreased after clonidine, 3.5 +/- 0.8 versus 2.4 +/- 0.8 %/mmHg (P < 0.05); this difference disappeared after restoration of MAP, 3.1 +/- 1.2 %/mmHg. With a 30-mmHg increase in MAP, Vm increased by 13% before and after clonidine (P < 0.05). CONCLUSIONS: Clonidine, 5 microg/kg orally, decreases Vm and slightly attenuates cerebral CO2 vasoreactivity, therefore decreased cerebral blood flow and mildly attenuated CO2 vasoreactivity should be anticipated.     

Cerebral blood flow velocity in relation to cerebral blood flow, cerebral metabolic rate for oxygen, and electroencephalogram analysis during isoflurane anesthesia in dogs

The purpose of this study was to correlate changes in cerebral blood flow velocity (Vmean) with cerebral blood flow (CBF) during isoflurane anesthesia in dogs. The relation between cerebral oxygen consumption (CMRO2) and electroencephalogram (EEG) analysis also was investigated. Blood flow velocity was measured in the middle cerebral artery using a pulsed transcranial Doppler (TCD). CBF was measured with radioactive microspheres. EEG was measured over both hemispheres and median EEG frequency (median frequency) was calculated after fast Fourier transformation. Baseline anesthesia was maintained with 50% nitrous oxide in oxygen and 50 micrograms.kg-1 x h-1 fentanyl. Animals of Group I (control, n = 6) were not given isoflurane. Data were recorded at baseline, and at 30, 60, and 90 min. There was no significant change in any variable over time. In Group II (n = 7), data were recorded at baseline and at 1%, 2%, and 3% end-tidal isoflurane. Mean arterial pressure was maintained at baseline levels by phenylephrine infusion. CBF increased from 70.8 +/- 10.6 mL.100g-1 x min-1 at baseline to 146.1 +/- 36.9 mL.100 g-1 x min-1 with 3% isoflurane (P < 0.01). Vmean increased from 38.3 +/- 6.7 cm/s to 65.6 +/- 9.7 cm/s (P < 0.01). The correlation between relative changes in CBF and Vmean was r = 0.94 (P < 0.01). With 1% isoflurane the EEG shifted to slow-wave, high-voltage activity, and median frequency decreased from 5.9 +/- 0.7 Hz to 1.4 +/- 0.4 Hz (P < 0.05). Median frequency was not decreased further during 2% and 3% isoflurane anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Treatment of mallet finger fractures by the extension-block K-wire technique

OBJECTIVES: This report describes successful anaesthesia and electroconvulsive therapy (ECT) in a patient with an unruptured basilar artery aneurysm. ECT is associated with a hyperdynamic state characterised by arterial hypertension, tachycardia, and considerably increased cerebral blood flow rate and velocity. These responses pose an increased risk for subarachnoid haemorrhage when an intracranial aneurysm coexists. METHODS: A 54 year old woman presented for ECT. She had a 20 year history of major depression which was unresponsive to three different antidepressant drugs. There was also an unruptured 5 mm saccular aneurysm at the basilar tip, which had been documented by cerebral angiography, but its size had remained unchanged for the previous four years. After she declined surgical intervention, she gave informed consent for ECT. During a series of seven ECT sessions middle cerebral artery flow velocity was recorded by a pulsed transcranial Doppler ultrasonography system. She was pretreated with 50 mg oral atenolol daily, continuing up to the day of the last ECT and immediately before each treatment, sodium nitroprusside was infused at a rate of 30 microg/min, to reduce systolic arterial pressure to 90-95 mm Hg. RESULTS: Systolic flow velocity during the awake state ranged from 62-75 cm/s, remaining initially unchanged with sodium nitroprusside infusion. After induction of anaesthesia (0.5 mg/kg methohexitone and 0.9 mg/kg succinylcholine), flow velocities decreased to 39-54 cm/s, reaching maximal values of 90 cm/s (only 20% above baseline) after ECT. These flow velocities recorded post-ECT were considerably below the more than twofold increase recorded when no attenuating drugs were used. Systolic arterial blood pressure reached maximal values of 110-140 mm Hg and heart rate did not exceed 66 bpm. Rapid awakening followed each treatment, no focal or global neurological signs were apparent, and the patient was discharged in remission. CONCLUSION: In a patient with major depression and a coexisting intracerebral saccular aneurysm who was treated with ECT, the combination of beta blockade with atenolol and intravenous infusion of sodium nitroprusside prevented tachycardia and hypertension, and greatly attenuated the expected increase in flow velocity in the middle cerebral artery.     

Helicobacter pylori eradication in the healing and recurrence of benign gastric ulcer: a two-year, double-blind, placebo controlled study

STUDY OBJECTIVE: To evaluate the safety and efficacy of monitored anesthesia care (MAC) in patients who undergo a novel treatment for hepatocellular cancer in which procedure-related hemodynamic instability is problematic. DESIGN: Nonrandomized open study. SETTING: University cancer center operating room. PATIENTS: Nine patients scheduled for hepatic arterial infusion of doxorubicin with complete hepatic venous isolation and extracorporeal chemofiltration (no more than 3 procedures per patient). INTERVENTIONS: Hepatic venous isolation was achieved with a dual-balloon inferior vena cava catheter connected to an extracorporeal circuit containing chemofilters. Doxorubicin was infused through the hepatic artery and filtered from the venous blood, which was returned to the patient through an internal jugular venous catheter. Each patient received a bolus of propofol (200 micrograms/kg) and one of alfentanil (2 micrograms/kg) followed by simultaneous infusions of propofol and alfentanil for percutaneous placement of the catheters and operation of the extracorporeal circuit. Drug rates were varied to maintain a sedative-analgesic state of calm, comfort, minimal movement, and adequate respiratory function. Prior to circuit initiation, patients were preloaded with crystalloid. During circuit operation, hypotension was treated with intravenous (IV) phenylephrine and crystalloid. MEASUREMENTS AND MAIN RESULTS: End-tidal CO2 (PETCO2), respiratory rate, oxygen saturation (SaO2), arterial blood pressure (BP), and heart rate (HR) were monitored. Systolic, diastolic, and mean arterial pressure (MAP), and HR were compared before, during, and after hepatic venous isolation and chemofiltration. Doses and infusion rates of propofol, alfentanil, and phenylephrine were recorded for each treatment. Hypotension occurred in 11 of 13 procedures when blood was directed through the chemofilters and was successfully treated with phenylephrine (dose range 40 to 5,733 micrograms) and crystalloid. Blood pressure returned to the baseline value on termination of the circuit. Throughout the sedation, patients were easily arousable, analgesia was adequate, and PETCO2 level of 38 +/- 4 mmHg and SaO2 greater than 94% were maintained. Mean doses and infusion rates of MAC drugs were, respectively: propofol, 261 +/- 88 mg and 23.7 +/- 3.6 micrograms/kg/min; alfentanil, 3,350 +/- 1,468 micrograms and 0.32 +/- 0.14 microgram/kg/min. CONCLUSIONS: Patients undergoing this novel cancer treatment are safely and effectively managed by MAC achieved with simultaneous infusions of alfentanil and propofol. Procedure-associated hypotension is easily treated with IV phenylephrine and crystalloid.     

Relationship between intrauterine growth retardation and early postnatal superior mesenteric artery blood flow velocity

During the first week of life, we examined the changes in the systemic, intestinal and cerebral circulation, and the circulatory responses to feeding in 10 small for gestational age (SGA) infants using the ultrasound Doppler technique. From day 1 to day 3, preprandial cardiac output decreased (p < 0.01), whereas mean blood pressure (p < 0.01), superior mesenteric artery mean flow velocity (Vmean; p < 0.01) and middle cerebral artery Vmean (p < 0.01) increased. On day 1, cardiac output was higher in the SGA than in those of term and preterm appropriate for gestational age infants reported from our laboratory. Preprandial superior mesenteric artery Vmean was inversely related to the degree of growth retardation (r = 0.63, p < 0.05). However, growth retardation did not influence the postprandial increase in superior mesenteric artery Vmean and end-diastolic flow velocity, or the cerebral circulation.     

Effects of magnesium sulphate on the noradrenaline-induced cerebral vasoconstrictor and pressor responses in the goat

OBJECTIVE: To examine the ability of magnesium sulphate to counteract the noradrenaline-induced cerebral vasoconstrictor and pressor responses in goats by using both in vivo and in vitro techniques. DESIGN: Cerebral blood flow was measured in vivo by means of an electromagnetic flow probe around the internal maxillary artery. Isometric tension was recorded in vitro from rings of goat middle cerebral artery maintained in an organ bath. RESULTS: 1. In vivo. Continuous infusion of noradrenaline (10 micrograms/min) directly into the cerebral arterial supply elicited sustained decrease in cerebral blood flow (61% [SEM 3] of control values) and increase in cerebral vascular resistance (178% [SEM 9] of control values). Magnesium sulphate, injected directly into the cerebral arterial supply (10-300 mg) or infused intravenously (0.3 g and 3 g during 15 min) at the noradrenaline-induced steady state, increased cerebral blood flow by decreasing cerebral vascular resistance in a dose-dependent manner. A similar result was obtained when intravenous magnesium sulphate (3 g/15 min) was tested against the cerebral vasoconstrictor and pressor responses induced by intravenous infusion of noradrenaline (30 micrograms/min). 2. In vitro. When compared with the response obtained in a control medium (1 mmol/L Mg2+), 10 mmol/L Mg2+ significantly inhibited the maximum contraction elicited by noradrenaline (10(-8) to 3 x 10(-3) mol/L) from 45% [SEM 4] to 26% [SEM 4]. CONCLUSIONS: Magnesium sulphate reverses the noradrenaline-induced cerebral vasoconstrictor and pressor responses by a direct inhibitory action of Mg2+ on the actions of noradrenaline in the cerebral and peripheral vascular beds, which leads to a decrease in vascular resistance. These results could explain, at least in part, the beneficial effects of magnesium sulphate in the management of preeclampsia and eclampsia.     

An attempt at reversibility and increase of the virulence of axenic strains of Entamoeba histolytica

Sequential changes of cerebral autoregulation were studied in 20 cats after recirculation of cerebral ischemia. The cerebral autoregulation was evaluated by autoregulation index (A.I.), calculating % delta cerebral blood flow (CBF)/delta cerebral perfusion pressure (CPP), with changing the mean arterial blood pressure (MABP) within 80-130 mmHg. Duration of ischemic insult was 15 min after disappearance of direct cortical response (DCR). Following recovery of cerebral circulation, MABP, CBF and intracranial pressure (ICP) were observed sequentially for at least 48 hours. In 6 of 20 cats the autoregulation was disturbed early after recirculation, and the ICP was increased, resulting in no cerebral blood flow (early deteriorated group). In the other 14 cats the autoregulation was restored immediately, but in 7 of the 14 cats it was disturbed again after 24 hours following recirculation (delayed deteriorated group), finally the ICP was elevated and the CBF became 0 as same as early deteriorated group. In another 7 cats it was not disturbed until 5 days. The changes in CBF following insult were five patterns. These were classified into type A (Gradual decrease), type B (Transient increase), type C (Constant maintenance), type D (Relatively rapid decrease) and type E (Rapid decrease). The delayed cerebral dysautoregulation occurred in the types except for type A and type E. These results suggested there was close relation between delayed dysautoregulation and delayed neuronal dysfunction that we reported previously. Moreover, we considered the delayed dysautoregulation could be speculated from the value of ICP/CBF immediately after recirculation and the pattern of the changes in CBF during ischemic insult.     

Differences in caries recording with and without bitewing radiographs. A study on 5-year old children in the County of Bohusl?n, Sweden

OBJECTIVE: To evaluate the cerebral blood flow parameters assessed by transcranial Doppler during aortic cross-clamping and unclamping in patients undergoing abdominal aortic aneurysmectomy. METHODS: Invasive intraoperative monitoring of mean arterial pressure (MAP) and PaCO2, and right middle cerebral artery (RMCA) monitoring of blood flow parameters (mean velocity "Vm" and pulsatility index "PI") by transcranial Doppler were performed as well as evaluation of the four parameters during these subsequent periods: pre-cross-clamping, pre-unclamping, unclamping and 1-5-10-20 minutes after abdominal aortic unclamping. RESULTS: No significative changes of MAP, PaCO2, Vm and PI were noticed during the aortic cross-clamping period (77.5 +/- 18.5 SD minutes). During aortic unclamping Vm and MAP decreased (64 +/- 20 vs 52 +/- 20 cm/sec, p < 0.05, and 101 +/- 8 vs 80 +/- 15 mmHg, p < 0.01, respectively). At the 1th post-unclamping minute there was an increase from pre-unclamping values of Vm (75 +/- 20 cm/sec, p < 0.05) and PaCO2 (42 +/- 1.5 vs 36 +/- 2 mmHg, p < 0.05), with persistent reduction of MAP (92 +/- mmHg, p < 0.05), even more evident at the 5th post-unclamping minute (Vm = 93 +/- 25 cm/sec; PaCO2 = 46 +/- 1.2 mmHg, p < 0.001, and MAP returned to pre-unclamping value), in which there was also a decrease of PI (0.65 +/- 0.16 vs 0.78 +/- 0.2, p < 0.05). At the 10th minute Vm (83 +/- 24 cm/sec, p < 0.02) and PaCO2 (41 +/- 1.5 mmHg, p < 0.05) increments were present together with persistent reduction of PI (0.69 +/- 0.17, p < 0.05), while at the 20th post-unclamping minute also Vm, PaCO2 and PI returned to their pre-unclamping values. CONCLUSIONS: The Vm decrease at aortic unclamping might correlate with the acute changes in MAP (blood steal hypovolemia) and is likely due to an inadequate cerebral autoregulatory response to abrupt MAP changes. The arterial CO2 increase after aortic unclamping could lead to a dilation of cerebral arterioles and a rise of CBF (increase of Vm and decrease of PI). Transcranial Doppler is a simple and reliable technique for the monitoring of cerebral blood flow parameters and seems to be quite suitable for the recognition and the quantification of changes in these parameters induced by surgical manoeuvres able to produce hemodynamic instability.     

Comparative effects of propofol, pentobarbital, and isoflurane on cerebral blood flow and blood volume

While intravenous and volatile anesthetics have widely differing effects on cerebral blood flow (CBF), clinical studies suggest that the relative differences in their effects on intracranial pressure (ICP) may be smaller. Because acute changes in ICP are determined primarily by changes in cerebral blood volume (CBV), we compared the impact of propofol, pentobarbital, and isoflurane on CBF and CBV in rats. Equipotent doses of the three agents were determined by tail-clamp studies. Animals were then anesthetized with propofol (20 mg/kg load, 38 mg.kg-1.h-1 infusion), pentobarbital (30 mg/kg load, 20 mg.kg-1.h-1 infusion), or isoflurane 1.6-1.8%. Two hours later, CBF and CBV were measured using 3H-nicotine as a CBF tracer, and 14C-dextran and 99mTc-labeled red cells as markers for cerebral plasma and red blood cell volumes (CPV and CRBCV), respectively. Total CBV was the sum of CPV and CRBCV. CBF was 2.0-2.6 times greater with isoflurane than with propofol or pentobarbital (137 vs. 67 and 52 ml.100 g-1.min-1, respectively). By contrast, while CBV was greater in the isoflurane group than in either the propofol or pentobarbital groups, the magnitude of the intergroup differences were much smaller (propofol = 2.49 +/- 0.28 ml/100 g; pentobarbital = 2.27 +/- 0.15 ml/100 g; isoflurane = 2.77 +/- 0.24 ml/100 g, mean +/- SD). These results suggest that the simple measurement of CBF may not adequately describe the cerebrovascular effects of an anesthetic, at least with respect to predicting the magnitude of the agents likely effects on ICP.     

Topical versus peribulbar anesthesia, without sedation, for clear corneal phacoemulsification

Electroconvulsive therapy (ECT) is an appropriate clinical model to investigate blood flow during seizures. In this study cerebral blood flow velocity (CBFV) was measured during 40 ECTs in 10 patients by means of transcranial Doppler sonography. EEG was recorded continuously. Under general anesthesia, the pre-convulsive blood flow velocity (Vmean) decreased significantly. After ECT, we measured a dramatic increase in Vmean which was significantly greater in the left MCA than in the right MCA. After termination of seizures, flow velocities returned to baseline levels. The striking increase in cerebral blood flow velocity reflects excessive cerebral metabolism during convulsive neuronal activation. The left hemisphere seems to be more sensitive to electrical stimuli as was indicated by its predominant augmentation of CBFVs.     

Effect of antenatal administration of thyrotrophin releasing hormone on fetal flow velocity waveforms

AIM: To determine whether antenatal administration of thyrotrophin releasing hormone (TRH), to promote lung maturation, alters blood flow through the fetal middle cerebral, umbilical artery, or ductus arteriosus and through the maternal uterine arteries. METHODS: The effect of transplacentally administered TRH on the fetal circulation was prospectively evaluated in 30 patients between 24 and 34 weeks' gestation. TRH (400 micrograms) was given to the mother intravenously either as a bolus or an infusion. Fetal effects were determined by measuring the maximum velocity and pulsatility index (PI) in middle cerebral artery, ductus arteriosus, uterine artery and umbilical artery Doppler waveforms. Measurements were made immediately before, and 10 and 60 minutes after maternal TRH administration. RESULTS: Intravenous injection of TRH had no significant effect on PI in the uterine, umbilical, or middle cerebral artery and the ductus arteriosus within 60 minutes of administration in either group. CONCLUSION: The antenatal use of TRH in conjunction with steroids for fetal lung maturity does not affect utero-placental or fetal haemodynamic variables, as measured by Doppler. These findings, therefore, do not support the suggestion that antenatal intravenous administration of TRH either as bolus or infusion may have immediate adverse vascular effects in the fetus.     

Changes in maternal middle cerebral artery blood flow velocity associated with general anesthesia in severe preeclampsia

In women with severe preeclampsia, significant increases in mean arterial pressures (MAP) are common after rapid induction of general anesthesia (GA) and tracheal intubation. The objectives of this prospective study were to assess the effects of the rapid induction-intubation technique on middle cerebral artery (MCA) flow velocity in severe preeclampsia and to examine the correlation between mean MCA flow velocity (Vm) and MAP. Eight women with severe preeclampsia (study group) and six normotensive women at term (control group) scheduled to undergo cesarean section under GA were studied. Before induction, patients in the study group received i.v. labetalol in divided doses to lower diastolic pressures to <100 mm Hg. Anesthesia was induced with pentothal 4-5 mg/kg, followed by succinylcholine 1.5 mg/kg to facilitate tracheal intubation. A transcranial Doppler was used to measure Vm. Both Vm and MAP were recorded before induction and every minute for 6 min after intubation. In the study group, after the administration of labetalol, MAP decreased from 129 +/- 9 to 113 +/- 9 mm Hg (P < 0.05), and Vm decreased from 59 +/- 11 to 54 +/- 10 cm/s (P < 0.05). After intubation, MAP increased from 113 +/- 9 to 134 +/- 5 mm Hg (P < 0.001), and Vm increased from 54 +/- 10 to 70 +/- 10 cm/s (P < 0.001). In the control group, while MAP increased significantly from 89 +/- 6 to 96 +/- 4 mm Hg (P < 0.05) after intubation, the concurrent increase in Vm from 49 +/- 5 to 54 +/- 7 cm/s was not significant. There was a significant positive pooled correlation between Vm and MAP (r = 0.5, P < 0.0006) in the study group but not in the control group (r = 0.24). After induction and intubation, both Vm and MAP values were significantly increased in the study group patients at all observation points compared with the control group patients. The findings indicate that Vm increases significantly after rapid-sequence induction of GA and tracheal intubation in women with severe preeclampsia, and there seems to be a direct relationship between MAP and Vm. Implications: In women with severe preeclampsia, rapid-sequence induction of general anesthesia and tracheal intubation can cause severe hypertension. Our results indicate that the increase in blood pressure is associated with a significant increase in maternal cerebral blood flow velocity and that there is a significant correlation between these two variables.     

A method for a simulation of continuous intracranial pressure curves

The study introduces a method to simulate continuously an intracranial pressure (ICP) wave form. In a system analysis approach the intracranial compartment was viewed as a black box with arterial blood pressure (ABP) as an input signal and ICP as an output. A weight function was used to transform the ABP curve into the ICP curve. The output ICP waveform was generated using a weight function derived from the transcranial Doppler blood flow velocity (FV) and ABP curves. In order to establish the relationship between TCD characteristics and weight functions simultaneous recordings of FV, ABP, and ICP curves of a defined group of patients were used. A linear function between the TCD characteristics and the weight functions was obtained by calculating a series of multiple regression analyses. Given examples demonstrate the procedure's capabilities in predicting the mean ICP, the pulse and respiratory waveform modulations, and the trends of ICP changes.     

Effects of solcoseryl on the cerebral blood flow, intracranial pressure, systemic blood pressure and EEG in acute intracranial hypertensive cats (author's transl)

The experiment was performed on 86 cases under intraperitoneal pentobarbital anesthesia. One balloon was placed in the extradural space of right frontal region, and the other balloon was placed in the left extradural space and the intracranial pressure was measured. A needle was stereotaxically inserted into the subcortical area in order to measure the cerebral blood flow. Systemic blood pressure was recorded by inserting a catheter into the femoral artery, and electrocorticogram was also recorded. An expanding intracranial lesion was made by inflating the extradural balloon with physiological saline. The animals were arbitrarily divided into two groups.: 1) light or moderate groups which intracranial pressure before the injection of drug was below 400 mmH2O. 2) severe groups above 400 mmH2O. After the maintenance of the pressure, Solcoseryl was infused intravenously. The investigation was focused to observe whether Solcoseryl reveales any potent effect on cerebral blood flow, intracranial pressure, systemic blood pressure and on electroencephalogram in acute intracranial hypertension. Results 1) Intravenous injection of Solcoseryl had the effect of lowering intracranial pressure in the light or moderate and severe groups. Particularly, dose of 80 mg/kg showed the marked effect, though with a rebound phenomenon in the light or moderate groups. Furthermore, the effect was more marked and lasting by drip infusion of Solcoseryl and also by intravenous injection of Solcoseryl after pretreatment with hydrocortisone, and at this time no rebound phenomenon was recognized. 2) Solcoseryl had the effect of increasing the cerebral blood flow accompained with the lowering of intracranial pressure. 3) Systemic blood pressure was transiently lowered by the injection of Solcoseryl 20 mg/kg or 80 mg/kg and recovered immediately. 4) Solcoseryl had no effect on electroencephalogram in the severe groups. Conclusion On the basis of these results, it is rational to conclude that Solcoseryl could be superior agent render to lower intracranial pressure and to improve cerebral blood flow in acute intracranial hypertension.     

Level concept of analgesic dosing in intensive care medicine with sufentanil

OBJECTIVE: The efficacy of a 3-level regimen of analgesia and sedation was investigated in a clinical setting. Level 1 consisted of continuous administration of sufentanil, in level 2 continuous administration of midazolam and level 3 continuous administration of midazolam and clonidine was added according to patients' needs. METHODS: Sufentanil at 1 microgram/kg/h was given initially. Later it was adjusted to patients' requirements in accordance with the Ramsay score (group 1). Long-term intubated patients received in addition midazolam 0.05 mg/kg/h (group 2). If needed, clonidine 1 microgram/kg/h was added (group 3). Mean drug requirements were investigated during controlled ventilation and during assisted ventilation with spontaneous breathing > 25% of total minute ventilation. In group 1 arterial paCO2 was measured to estimate drug-induced respiratory depression. Values given are median and ranges. RESULTS: With the 3-level-regimen of analgesia and sedation a Ramsay score of 2-3 was achieved in all intensive-care patients. In group 1 (n = 109; 36.7%) paCO2 values were similar at all times. Patients on controlled ventilation needed sufentanil 0.6 (0.075-2.5) microgram/kg/h, on assisted ventilation 0.4 (0.05-2.5) microgram/kg/h. Patients of group 2 (n = 113; 38.1%) had on controlled ventilation a higher requirement of sufentanil 1.2 (0.09-2.7) micrograms/kg/h, in addition Midazolam 0.05 (0.002-0.56) mg/kg/h was given. On assisted ventilation with spontaneous breathing > 25% sufentanil 0.9 (0.05-2.6) microgram/kg/h plus midazolam 0.04 (0.002-0.38) mg/kg/h was sufficient. Group 3 (n = 75; 25.2%) had on controlled ventilation a higher requirement of sufentanil with 1.5 (0.09-4.0) micrograms/kg/h and midazolam 0.05 (0.005-0.52) mg/kg/h, in addition clonidine 1.1 (0.12-2.88) micrograms/kg/h was given. On assisted ventilation with spontaneous breathing > 25% requirement of sufentanil with 1.1 (0.15-2.6) micrograms/kg/h and of midazolam with 0.05 (0.002-0.22) mg/kg/h was slightly lower, whereas more clonidine was needed with 1.3 (0.12-2.88) micrograms/kg/h. CONCLUSION: Continuous infusion of sufentanil only for analgesia and sedation is suitable for intensive-care patients with a short stay in the ICU. Respiratory depression during spontaneous breathing is not significant. The supplementary administration of midazolam and clonidine according to the presented regimen was shown to be of advantage for patients with a longer stay in ICU.     

Total intravenous anaesthesia with sufentanil-midazolam for major abdominal surgery

Haemodynamic and endocrine stress responses were compared during total intravenous anaesthesia with sufentanil and midazolam or fentanyl and midazolam in patients undergoing elective major abdominal surgery. Twenty-two ASA I and II patients were allocated randomly to receive sufentanil (induction 1.5 micrograms kg-1 plus infusion 1.5 micrograms kg-1 h-1) or fentanyl (induction 10 micrograms kg-1 plus infusion 10 micrograms kg-1 h-1) supplemented with 0.15 microgram kg-1 sufentanil or 1 microgram kg-1 fentanyl as necessary. Midazolam was infused to obtain plasma concentrations of 500-600 ng ml-1. Ventilation was with oxygen-enriched air. The opioid infusion was reduced post-operatively by half and benzodiazepine effects were reversed by titration with flumazenil. Mean arterial pressure, heart rate and cardiac index decreased in both groups after induction (cardiac index: sufentanil 4.94 +/- 0.45 to 2.99 +/- 0.18 litre min-1; fentanyl 4.97 +/- 0.45 to 3.71 +/- 0.36 litre min-1), but all returned to baseline during surgery. With sufentanil; mean arterial pressure was lower throughout the study period, and heart rate was lower intra-operatively. Oxygen uptake decreased in both groups after induction (sufentanil 289 +/- 29 to 184 +/- 21 ml min-1; fentanyl 318 +/- 32 to 216 +/- 32 ml min-1) and remained low with sufentanil until flumazenil was given. Adrenaline concentrations increased in both groups but there was no intergroup difference. The median noradrenaline concentration was lower intra-operatively with sufentanil (0.47 nmol litre-1 (range 0.06-6.77)) than with fentanyl (0.73 nmol litre-1 (0.07-4.58)). Cortisol, glucose and lactate concentrations increased in both groups. Bradycardia occurred in four patients with sufentanil and in three with fentanyl. There were two cases of marked thoracic rigidity with sufentanil and one with fentanyl.