Improvement of arterial oxygenation by selective infusion of prostaglandin E1 to ventilated lung during one-lung ventilation

Background:One-lung anesthesia provides a better surgical field for thoracic procedures but also impairs the arterial oxygenation and venous admixture. During one-lung ventilation, pulmonary vasoconstriction is assumed to be present within both ventilated and collapsed lungs. We propose that arterial oxygenation could be optimized by offsetting the vasoconstriction within the microcirculation of ventilated lung. Method:In an anesthetized dog model, incremental doses of prostaglandin E₁ (PGE₁) were selectively infused into the main trunk of the pulmonary artery of the ventilated lung after one-lung ventilation for 60 min (PGE₁ group, n=9). Arterial oxygenation and calculated venous admixture (Qs/Qt) was also assessed in a time-course control group (Control group, n =5). During two-lung ventilation (FIO₂: 0.66), arterial PO₂ and venous admixture was 44.22 ± 3.5 kPa and 10.7±2.3%, respectively. One-lung ventilation (FIO₂: 0.66) with left lung collapsed reduced arterial PO₂ to 11.6±1.7 kPa and increased venous admixture to 40.7±5.8% (P<0.001). Venous O₂ tension also decreased from 6.3±0.7 kPa to 5.0±0.6 kPa with a slight increase in mean pulmonary artery pressure and pulmonary vascular resistance (P <0.05). Results: During selective infusion of PGE₁ at a dose of 0.04 to 0.2 μg kg^-1 min^-1, there was a dose-dependent improvement in arterial PO₂ with a parallel reduction of venous admixture during one-lung ventilation. Arterial PO₂ increased to a maximum of 23.0±4.3 kPa, and the venous admixture decreased significantly to a minimum of 27.4±4.2% by PGE₁ at a dose of 0.04-0.4 μg kg^-1 min^-1 (P<0.01). PGE₁ resulted in a small increase in cardiac output and decreases of pulmonary pressure and pulmonary vascular resistance at a relatively high dose of 0.4 μg kg^-1 min^-1 during selective infusion (P<0.05). Conclusion: These results suggest that a selective pulmonary artery infusion of PGE₁ to the ventilated lung within the dose range of 0.04-0.4 μg kg^-1 min^-1 is practical and effective to improve arterial oxygenation and reduce venous admixture during one-lung ventilation.     

Hemodynamic effects of dobutamine and dopexamine after cardiopulmonary bypass in pediatric cardiac surgery*

Background: After surgical repair of congenital heart disease, inotropic support is sometimes necessary to wean from cardiopulmonary bypass. In pediatric cardiac surgery, dobutamine and dopamine are often used as inotropic support. Dopexamine is a synthetic catecholamine, which has positive inotropic and vasodilating properties. Because the hemodynamic effects of catecholamines are modified after cardiopulmonary bypass, the aim of this study was to investigate the effects of dobutamine and dopexamine on cardiac index and systemic vascular resistance index after cardiopulmonary bypass in pediatric cardiac surgery. Methods: The study was performed in a prospective, randomized, and double‐blinded cross‐over design. The investigation included 11 children for elective, noncomplex congenital heart surgery. After weaning from cardiopulmonary bypass and a 20‐min period of steady state, children received either 2.5 μg·kg^?1·min^?1 dobutamine or 1 μg·kg^?1·min^?1 dopexamine for 20 min. Cardiac index (transpulmonary thermodilution), mean arterial pressure, central venous pressure, stroke volume, systemic vascular resistance, and central venous oxygen saturation were determined. The primary outcome variable was cardiac index. Results: No difference in cardiac index was observed between the two groups (P = 0.594). Both drugs increased cardiac index, dopexamine from 3.9 ± 0.6 to 4.7 ± 0.8 l·min^?1·m^?2 (P = 0.003) and dobutamine from 4.1 ± 0.7 to 4.8 ± 0.7 l·min^?1·m^?2 (P = 0.004). During treatment with dobutamine, children presented with significantly higher mean arterial pressure (P = 0.003) and systemic vascular resistance index (P = 0.026). Conclusions: This trial demonstrates that low‐dose dobutamine and dopexamine both increase cardiac index during pediatric cardiac surgery but with different hemodynamic effects.     

Prolonged mivacurium infusion in young and elderly adults

Purpose

This study was designed to evaluate phanmacodynamically and phamnacokinetically if the cis-cis isomer of mivacurium contributed to neuromuscular block during prolonged infusions lasting more than four hours in young adult and elderly (> 60 yr) patients.

Methods

The mechanomyogramic neuromuscular response of the adductor pollicis was recorded in 32 adults 18–59 yr. and 19 elderly (> 60 yr.) patients dunng N₂O:O₂:opioid anaesthesia. The mivacurium infusion rate was adjusted to maintain single twitch depression at 95 ± 4% of control. Blood samples were taken every 30 min to determine the plasma concentration of cis-cis isomer of mivacurium. At the end of the surgical procedure, patients were allowed to recover spontaneously to at least 25% of control twitch response.

Results

The mean mivacurium infusion requirement to maintain 97 ± 1 (mean ± SD)% depression of the twitch response was 6.0 ± 0.4 μg· kg^?1· min^?1 in young adults, and 4.3 ± 0.3 μg· kg^?1· min^?1 in elderly patients (P < 0.001). The infusion requirement in patients with low plasma cholinesterase activity was the lowest 2.4 ± 1.2 μg· kg^?1· min^?1. Plasma cis-cis isomer concentrations reached peak levels within one-two hours and remained relatively constant throughout the duration of infusion even in patients with tow cholinesterase activity. There was no relationship between duration of infusion, plasma concentrations of cis-cis isomer and the early recovery indices of mivacurium (up to 25%). Neuromuscular transmission recovered adequately with or without antagonism in all patients.

Conclusion

When the mivacurium infusion was titrated to maintain 95 ± 4% twitch depression, the plasma concentration of the cis-cis isomer did not increase during prolonged infusions (four hours) and neuromuscular transmission recovers satisfactorily.     

Mivacurium infusion requirements following vecuronium: different response between adults and children

The mivacurium infusion requirements following vecuronium were evaluated in 15 adults and 15 children in an open prospective clinical study. This study was undertaken to elucidate whether potentiation of effect occurred when a mivacurium infusion was administered after vecuronium was used for the facilitation of tracheal intubation. The adult patients were anaesthetized with N₂O:O₂, propofol and fentanyl, the children with halothane (1%) N₂O:O₂ Vecuronium 100 μg · kg^?1 was administered during stimulation of the ulnar nerve with train-of-four stimuli at 0.1 Hz. The force of contraction of the adductor pollicis was recorded. Upon recovery of the twitch response from vecuronium, a mivacurium infusion was started at 4 μg · kg^?1 · min^?1, thereafter adjustments were made to maintain the first twitch of the train-of-four (T₁ at 1–10% of control. The mean (±SE) initial infusion requirements in children of mivacurium was 4.3 (0.4) μg · kg^?1 · min^?1 which increased linearly (P < 0.001) over the next 90 min to 10 μg · kg^?1 · min^?1. In adults the infusion requirement was lower than in children and remained at approximately 3 μg · kg^?1 · min^?1 over the next 75 min. At the end of the surgical procedure, the children recovered faster than the adults with no child requiring reversal. Because of prolonged recovery (>20 min), seven adults required reversal with 15–70 μg · kg^?1 neostigmine. Mivacurium infusion requirements following vecuronium are higher in children than adults. Potentiation of the effects of mivacurium were seen when vecuronium preceeded mivacurium. This potentiation of effect lasted longer in adults than in children.     

Auswirkungen von Dopexamin Transpulmonales Shuntvolumen bei thorax- chirurgischen Eingriffen mit Ein-Lungen-Beatmung

Objective: To study the influence of dopexamine on pulmonary shunt and hypoxic pulmonary vasoconstriction during major thoracic surgery with one-lung ventilation (OLV). Design: Prospective, randomised, placebo-controlled study. Setting: University hospital. Patients: Twenty adult patients undergoing elective pulmonary resection. Anaesthesia: General anaesthesia was performed using propofol, fentanyl, N₂O and vecuronium.Volume-controlled ventilation was performed to maintain normocapnia over the whole investigation period. During OLV, the tidal volume was reduced and the respiratory rate was increased to avoid a peak airway pressure exceeding 40 cm H₂O. Furthermore the FiO₂ was increased to 1,0 and the external PEEP was removed during OLV. Interventions: The patients received either dopexamine at 2 µg/kg/min (group A, n=10) or 0,9% saline as control (group B, n=10) after assessing the baseline values. Measurement and results: The following cardiorespiratory variables were recorded: Heart rate, mean arterial pressure and mean pulmonary arterial pressure. Cardiac output was measured by thermodilution using a continuous cardiac output thermodilution catheter. Arterial and mixed venous blood gas analysis were measured from simultaneously drawn samples. Cardiac index (CI), systemic vascular resistance index, pulmonary vascular resistance index, oxygen delivery index (DO₂I), oxygen consumption index and the venous admixture were calculated using standard formula. Furthermore, pressure-flow-curves were constructed to analyse flow independent changes in the pulmonary vascular resistance. Data were recorded at the following times: After induction of anaesthesia in stable haemodynamics during two-lung ventilation (baseline values, T0), intraoperatively during one-lung ventilation (T1) and postoperatively after re-establishing two-lung ventilation (T2). Patients characteristics, data from the preoperative lung function testing and surgical procedures did not differ significantly between the groups. CI increased in the dopexamine group from 2,5±1,2 l·min^?1·m^?2 (T0) to 3,6±0,9 l·min^?1·m^?2 (T1) and 4,0±1,3 l·min^?1· m^?2 (T2). The course of the intrapulmonary right-to-left shunting did not differ between the groups. In the dopexamine-treated group the DO₂I increased from 430±143 ml·min·m^?2 (T0) to 652±255 ml·min·m^?2 (T1) and 653±207 ml·min·m^?2 (T2). Regarding the pressure-flow-curves there was no difference during OLV between the two groups indicating no major blocking effect of dopexamine on hypoxic pulmonary vasoconstriction. Conclusion: It is concluded that dopexamine can be used to improve haemodynamics and oxygen delivery during thoracic surgery without increasing venous admixture during one-lung ventilation.     

Intrathecal clonidine decreases propofol sedation requirements during spinal anesthesia in infants

Background: Propofol is a popular agent for providing procedural sedation in pediatric population during lumbar puncture and spinal anesthesia. Adjuvants like clonidine and fentanyl are administered intrathecally to prolong the duration of spinal anesthesia and to provide postoperative analgesia. We studied the propofol requirement after intrathecal administration of clonidine or fentanyl in infants undergoing lower abdominal surgeries. Methods: Sixty‐five ASA I infants undergoing elective lower abdominal surgery under spinal anesthesia were assigned into four groups in this prospective randomized double‐blinded study. Group B received bupivacaine based on body weight (<5 kg = 0.5 mg·kg⁻¹; 5–10 kg = 0.4 mg·kg⁻¹). Group BC received 1 μg·kg⁻¹ of clonidine with bupivacaine, group BF received 1 μg·kg⁻¹ of fentanyl with bupivacaine, and patients in group BCF received 1 μg·kg⁻¹ each of clonidine and fentanyl with bupivacaine. A bolus of 2–3 mg·kg⁻¹ of propofol bolus was administered for lumbar puncture. Sedation was assessed using a six‐point sedation score (0–5) and a five‐point reactivity score (0–4) which was based on a behavioral score. After achieving a sedation and reactivity score of 3–4, the patients were placed lateral in knee chest position and lumbar puncture performed and test drug administered. Further intraoperative sedation was maintained with an infusion of 25–50 μg·kg⁻¹·min⁻¹ of propofol infusion. Results: The mean ± sd infusion requirement of propofol decreased from 35.5 ± 4.5 in group B to 33.4 ± 5.4 μg·kg⁻¹·min⁻¹ in group BF and further decreased to 16.7 ± 6.2 μg·kg⁻¹·min⁻¹ and 14.8 ± 4.9 μg·kg⁻¹·min⁻¹ in group BC and BCF, respectively. There were no statistically significant differences between BC and BCF groups. The mean sedation and reactivity scores were higher in groups BC and BCF when compared to groups B and BF. Conclusion: Our study show that the requirement of propofol sedation reduces with intrathecal adjuvants. The reduction was significant with the addition of clonidine and clonidine–fentanyl combination as opposed to bupivacaine alone or with fentanyl. There was no significant difference in propofol infusion requirement with the use of bupivacaine alone or with fentanyl.     

Changes in carbon dioxide tension and oxygen saturation during deep sedation for paediatric cardiac catheterization

The purpose of this observational study was to determine whether hypercarbia or oxygen desaturation occurred during our current regimens of deep sedation or general anaesthesia of infants and children undergoing cardiac catheterization. Data were gathered prospectively from 50 consecutive infants and children aged 4 months to 12 years undergoing cardiac catheterization. Several anaesthetists used the following regimens, which were not randomized: 1) propofol. 1.5–2.0 mg·kg^?1 and fentanyl 1 μg·kg^?1 IV over 2 min for induction, followed by propofol infusion of 100–150 μg·kg^?1·min^?1; 2) fentanyl 2–3 μg·kg^?1 and midazolam 0.1–0.2 mg·kg^?1 IV over 10–15 min; 3) ketamine 8 mg·kg^?1 IM, or 4) same as regimens 1 or 2, plus pancuronium, intubation and controlled ventilation. Regimens 1, 2, and 3 were associated with spontaneous ventilation through the natural airway. End-tidal carbon dioxide tension (Petco₂), Spo₂, and respiratory rate were monitored for 60 min. The three regimens employing spontaneous ventilation through the natural airway were associated with both statistically and clinically significant increases in Petco₂ and decreases in Spo₂. This raises the possibility that acute exacerbation of PAP and PVR may occur in pulmonary hypertensive patients. In contrast, Petco₂ and Spo₂ did not change significantly from baseline in the controlled ventilation group.     

Comparison of fentanyl,sufentanil and alfentanil during awake craniotomy for epilepsy

Neurolept anaesthesia is used during awake craniotomy for epilepsy surgery. This study compares analgesia, sedation and the side effects of the newer opioids sufentanil and alfentanil, with those of fentanyl in patients undergoing awake craniotomy. Thirty patients were randomized into three groups, each received droperidol, dimenhydrinate and the chosen opioid as a bolus followed by an infusion. The opioid doses used were fentanyl 0.75 μg · kg^?1 plus 0.01 μg · kg^?1 · min^?1; sufentanil 0.075 μg · kg^?1 plus 0.0015 μg · kg^?1 · min^?1, and alfentanil 7.5 μg · kg^?1 plus 0.5 μg · kg^?1 · min^?1. There were no differences in the requirements for droperidol, dimenhydrinate or in the incidence of complications among the three groups. The total doses of the opioids required were fentanyl 4.9 ±1.3 μg · kg^?1, sufentanil 0.6 ±0.2 μg · kg^?1 and alfentanil 149 ±36 μg · kg^?1. Two patients became uncooperative requiring general anaesthesia. The conditions for surgery, electrocorticography and for stimulation testing were satisfactory in all other patients. We conclude that the newer opioids did not offer any benefit over fentanyl.     

Effects of dopamine, dopexamine and dobutamine on renal excretory function during experimental sepsis in conscious rats

Background: Acute renal failure is a frequent complication in human sepsis. Various inotropic drugs are often used to improve central haemodynamics and renal function. The differential preservative role of the most commonly used inotropic drugs on renal function, in this condition, has previously not been extensively studied. The aim of this experimental animal study was therefore to compare the preserving effects of dopamine, dopexamine, dobutamine and saline on renal excretory function, after induction of sepsis in conscious rats. Method: The effects of dopamine (DA) (2.5 μg · kg^-1 · min^-1; n= 11), dopexamine (DX) (1 μg·kg^-1· min^-1; n=10), dobutamine (DB) (5 μg·kg^-1· min^-1; n=10) and saline (n=13) on the glom-erular filtration rate (GFR), urine flow (UF), sodium excretion (SE) and fractional urinary excretion of sodium (FUE_Na) were studied and compared in conscious rats subjected to a 1-h infusion of live E. coli bacteria (10⁹/h). Results: In the saline-treated control group, bacteria infusion decreased GFR, UF, SE and FUE_Na by 31%, 53%, 51% and 36% respectively, associated with a 16% decrease in mean arterial pressure (MAP), and a 10% increase in heart rate (HR). In the post-E. coli treatment period, the fall in MAP was less pronounced with DX compared to both DB and control, while there was no difference between DX and DA. The increase in HR was most pronounced with DB. GFR decreased to a lesser extent with DX compared to DA, DB and control. UF and SE were better maintained with DX compared to DB and control, while there was no difference in FUE_Na between the groups. Conclusion: We conclude that dopexamine, to a greater extent than dopamine and dobutamine, improves renal excretory function in experimental septic shock.     

Optimizing sedation following major vascular surgery: a double-blind study of midazolam administered by continuous infusion

A randomized, double-blind study was undertaken to determine the dose requirements, recovery characteristics, and pharmacokinetic variables of midazolam given by continuous infusion for sedation in patients following abdominal aortic surgery. Thirty subjects, 50–75 yr, scheduled to undergo aortic reconstructive surgery, entered the study. Following a nitrous oxide-isoflurane-opioid anaesthetic technique, patients were randomly allocated to receive one of three loading doses (0.03, 0.06 or 0.1 mg · kg^?1) and initial infusion rates (0.5, 1.0 or 1.5 μg · kg^?1 · min^?1) of midazolam, corresponding to groups low (L), moderate (M) and high (H). The infusion of midazolam was adjusted to maintain sedation levels of “3, 4 or 5,“ which permitted eye opening in response to either verbal command or a light shoulder tap, using a seven-point scale ranging from “0” (awake, agitated) to “6” (asleep, non-responsive). Additionally, morphine was given in increments of 2.0 mg iv prn for analgesia. On the morning after surgery, midazolam was discontinued, and the tracheas were extubated when patients were awake. Blood samples were taken during, and at increasing intervals for 48 hr following discontinuation of the infusion, and analyzed by gas chromatography. The desired level of sedation was maintained during more than 94% of the infusion period in all three groups, with a maximum of three dose adjustments per patient, for treatment which lasted 16.3 ± 0.6 hr. There was, however, an increase in both the infusion rates and mean plasma concentrations from Group L to Group H (P < 0.05), which corresponded to an inverse relationship of morphine requirements during the period of sedation (P < 0.05, Group H vs Group L). Optimal midazolam infusion rates and resulting plasma concentrations at the times the infusions were discontinued (in parentheses) were as follows — Group L: 0.60 ± 0.18 μg · kg^?1 min^?1 (76 ± 32 ng · mL^?1), Group M: 0.90 ± 0.52 μg · kg^?1 · min^?1 (133 ± 71 ng · mL^?1), and Group H: 1.34 ± 0.69 μg · kg^?1 · min^?1 (206 ± 106 ng · mL^?1). Times to awakening were longer in Group H: 3.1 ± 3.4 hr, than in Group L: 1.1 ± 0.8 h, P < 0.05. Pharmacokinetic variables were found to be dose- independent over the range of infusion rates. Mean values were t_1/2β = 4.4 ± 1.5 hr, CL = 5.94 ± 1.69 mL · min^?1 · kg^?1, Vd = 3.13 ± 1.07 L · kg^?1. It is concluded that midazolam, infused between 0.6–0.9 μg · kg^?1 · min^?1, provides a stable level of sedation, when administered in conjunction with intermittent iv morphine following AAS. This sedation technique, which costs $1.65 ± 0.73 hr^?1 ($Can), is associated with rapid recovery and minimal side effects.     

The inhibitory effect of esmolol on human plasmacholinesterase

Esmolol, a new cardioselective beta adrenergic blocker inhibits plasmacholinesterase activity in vitro. The concentration of esmolol hydrochloride that inhibits by 50 per cent the hydrolysis of 50.0 µnol·L^?1 benzoylcholine hydrochloride by 1:200 diluted, heparinized pooled plasma of six healthy volunteers at 37° C and 240 nm, determined by the ultraviolet spectrophotometric method of Kalow, was 50 µmol·^?1. Esmolol’s primary metabolite, 3-(4-(2-hydroxy-3-(isopropylamino)propoxy)-phenyllpropionic acid, had an l₅ = 190 µnol·L^?1 . The benzoylcholine hydrolysis rates in the plasma of ten patients who received an esmolol infusion of 500 µg·kg^?1. min^?1 for 4 minutes were 58.6 ± 6.2 µmol·hr^?1·ml^?1 (mean ± SE) before and 55.1 ± 6.6 µmol·hr^?1·ml^?1 after the infusion. The benzoylcholine hydrolysis rates in the plasma of ten patients who received an esmolol infusion of 500 µg·kg^?1·min^?1 for two minutes and 200 µg·kg^?1·min^?1 for an additional two minutes were 70.2 ± 8.9µmol·hr^?1·ml^?1 before and 69.1 ± 9.5 µmol·hr^?1. ml^?1 after the infusion. The pre- and post-infusion plasmacholinesterase activities were not significantly different. Since plasmacholinesterase is responsible for the hydrolysis of succinylcholine and that of the ester-type local anaesthetics this lack of in vivo interaction of esmolol with the hydrolysis of these drugs should be further confirmed by experiments with these combinations in man.     

Postoperative junctional ectopic tachycardia

Purpose

To report the management of junctional ectopic tachycardia after cardiac surgery in an infant. Postoperatively, the patient suffered profound cardiac decompensation secondary to the accelerated rhythm and required extracorporeal membrane oxygenation (ECMO) for haemodynamic support.

Clinical features

A 14-day-old, 3.5 kg boy exhibited junctional ectopic tachycardia after cardiopulmonary bypass. Left atrial pressure was 25–28 mmHg. No impact on the tachycardia was seen after rapid overdrive atrial pacing or after 20 μg fentanyliv, 45 μg digitalis, 100 mg magnesium or procainamide (loading dose 15 mg, then 30 mg·kg^?1·min^?1). Active cooling decreased the nasopharyngeal temperature to 35.2°C, when the heart rate decreased below 180 bpm with a left atrial pressure of 8–10 mmHg. Dopamine (2 μg·kg^?1·min^?1) and dobutamine (5 μg·kg^?1·min^?1) were added to improve the cardiac output. Sodium nitroprusside (0.25 to I μg·kg^?1·min) maintained the systolic pressure <100 mmHg. On arrival in ICU, heart rate increased to 200 bpm. The patient received cardiac massage for severe hypotension 75 min after surgery. Emergency ECMO was instituted for circulatory support. Procainamide, digoxin, dopamine, dobutamine, sodium nitroprusside and hypothermia were continued. Sinus rhythm resumed on the first postoperative day, but procainamide and induced hypothermia at 34°C were maintained for 36 hr after normalization of the rhythm to prevent recurrence of the tachycardia. Total duration of ECMO was three and a half days. Recovery was uneventful.

Conclusion

The use of ECMO, as a first line of defence, is suitable for the emergency support of patients with JET because of the ease of support of circulation and precise control of hypothermia.     

40 Hz Auditory steady-state response and EEG spectral edge frequency during sufentanil anaesthesia

Purpose

The auditory steady-state evoked response (ASSR) is an evoked potential which provides a sensitive measure of the effects of general anaesthetics on the brain. We used pharmacokinetic-pharmacodynamic (PK-PD) modelling to compare the effects of sufentanil on the amplitude of the ASSR with its effect on spectral edge frequency (SEF) of the electroencephalogram.

Methods

Nine patients scheduled for elective cardiac surgery participated. Midazolam (70 μg·kg^?1 im) was given 60 min before entering the operating room. Anaesthesia was induced with 5 μg·kg^?1 sufentanil at a rate of 0.83 μg·kg^?1·min^?1. The ASSR, SEF and plasma sufentanil concentrations were measured for 30 min ater induction of anaesthesia before surgery. The half-life between the central and effect site compartments (t_1/2K_eo), the 50% inhibitory concentration (IC₅₀) and the slope factor (gamma) were computed.

Results

The amplitude of the ASSR increased during the first three minutes of infusion of sufentanil by up to 40%. This was followed by a rapid decrease between the fourth and fifth minutes to 16% of baseline. The SEF decreased progressively during the first five minutes of infusion to 18% of baseline. Both measures subsequently showed modest recovery. The parameters gamma, IC₅₀ and t_1/2K_eofor ASSR were (mean ±SD) 6,0 ±3.7, 2.1 ±1,2 ng·ml^?1 and 7.3 ±2.4 min. For SEF the values were 5.9 ±5.2, 1.4 ±0.7 ng·ml^?1 (P < 0.05 compared with ASSR) and 6.8 ±2,4 min.

Conclusion

The sensitivity of ASSR to sufentanil is less than that of the SEF.     

The effect of dopamine,atropine, phenylephrine and cardiac pacing on oxygen consumption during fentanyl-nitrous oxide anaesthesia in the dog

In animals deeply anaesthetized with fentanyl and nitrous oxide the artierial blood pressure and heart rate were increased using dopamine, atropine, electrical pacing and phenylephrine in order to study the accompanying change in whole body oxygen consumption. Seven dogs (16–24 kg) were anaesthetized with fentanyl 1 μg · kg^-1 · min^-1. After completing instrumentation a dopamine infusion was started at a rate of 39 μg · kg^-1 · min^-1. After the mean blood pressure reached 18.6 kPa the infusion was reduced to 10 μg · kg^-1 · min^-1 and maintained for 10 minutes. After waiting 45 minutes an infusion of atropine 20 μg · kg^-1 · min^-1 was started and when the heart rate reached 120 b/min the infusion was slowed to 1.25 μg · kg^-1 ’ · min^-1 and maintained for 10 minutes. Twenty-five minutes later the heart rate was increased to 150 beats/min and maintained at that level for 10 minutes using electrical pacing. The pacing was removed and an infusion of phenylephrine 5 μg·kg^-1·min^-1 was started. When the blood pressure reached 21.3 kPa the infusion was reduced to 2.5 μg · kg^-1· min^-1 and maintained for 10 minutes. The results show increases in oxygen consumption of 14 per cent with dopamine, 19 per cent with atropine, 16 per cent with pacing, and 14 per cent with phenylephrine. All changes were significantly different from the control values. The magnitude of change in whole body oxygen consumption was best predicted by either the cardiac output x blood pressure product or by the cardiac output alone.     

Réponse ventilatoire à l'hypercapnie et à l'hypoxie hypocapnique du chien sous différents niveaux d'anesthésie à l'Alfatésine

The authors have studied the response to hypercapnia and hypocapnic hypoxia in nine dogs anesthetised with Althesin, in correlation with three levels of anaesthesia defined by three different anaesthetic flow rates (A = 6.57 ± 2.00 μl . kg^?1 . min^?1; B = 13.88 ± 2.87 μl . kg^?1 . min^?1; C = 19.53 ± 5.34 μl . kg^?1 . min^?1). The animals were intubated. Ventilation was measured by means of a pneumotachograph. Arterial blood gases (pHa, PaCO₂, PaO₂) were measured before and at the end of each hypercapnia and hypocapnic hypoxia test. The results were compared with data in the literature concerning the dog awake. Increasing depth of anaesthesia leads to worsening hypoventilation and hypercapnia. As with other anaesthetic agents, the response to hypercapnia is more depressed the deeper the anaesthesia. On the other hand, unlike what has been described with other anaesthetic agents, hypoxia stimulates ventilation; the response to hypoxia is not abolished by the deeper states of anaesthesia. The possible mechanisms of this difference are discussed.     

Determination of the pharmacodynamic interaction of propofol and dexmedetomidine during esophagogastroduodenoscopy in children

Objectives: Propofol is a sedative‐hypnotic drug commonly used to anesthetize children undergoing esophagogastroduodenoscopy (EGD). Dexmedetomidine is a highly selective alpha‐2 adrenergic receptor agonist that has been utilized in combination with propofol to provide anesthesia. There is currently no information regarding the effect of intravenous dexmedetomidine on the propofol plasma concentration–response relationship during EGD in children. This study aimed to investigate the pharmacodynamic interaction of propofol and dexmedetomidine when used in combination for children undergoing EGD. Methods: A total of 24 children undergoing EGD, ages 3–10 years, were enrolled in this study. Twelve children received dexmedetomidine 1 μg·kg^?1 given over 10 min as well as a continuous infusion of propofol delivered by a computer‐assisted target‐controlled infusion (TCI) system with target plasma concentrations ranging from 2.8 to 4.0 μg·ml^?1 (DEX group). Another group of 12 children undergoing EGD also received propofol administered by TCI targeting comparable plasma concentrations without dexmedetomidine (control group). We used logistic regression to predict plasma propofol concentrations at which 50% of the patients exhibited minimal response to stimuli (EC₅₀ for anesthesia). Results: The EC₅₀ ± se values in the control and DEX groups were 3.7 ± 0.4 μg·ml^?1 and 3.5 ± 0.2 μg·ml^?1, respectively. There was no significant shift in the propofol concentration–response curve in the presence of dexmedetomidine. Conclusion: The EC₅₀ of propofol required to produce adequate anesthesia for EGD in children was unaffected by a concomitant infusion of dexmedetomidine 1 μg·kg^?1 given over 10 min.     

Prostaglandin E1 attenuates the hypertensive response to tracheal extubation

Purpose

Tracheal extubation causes hypertension and tachycardia, which may cause imbalance between myocardial oxygen demand and supply in patients at risk of coronary artery disease. We conducted a randomized, controlled study to evaluate the effects of 0.05 or 0.1 μg · kg^?1 · min^?1 prostaglandin E₁, (PGE₁) iv on haemodynamic variables occurring during tracheal extubation and emergence from anaesthesia and compared them in patients receiving either lidocaine or saline.

Methods

Eighty ASA physical status I patients undergoing elective surgery were enrolled in the current study. Anaesthesia was maintained with sevoflurane 1.0%–2.5% (ET concentration) and nitrous oxide 60% in oxygen. Muscle relaxation was achieved with vecuronium. The patients were randomly assigned to receive one of four treatments (n = 20 each): saline (control), 0.05 μg · kg^?1 · min^?1 PGE₁, 0.1 μg · kg^?1 · min^?1 PGE₁, or 1 mg · kg^?1 lidocaine. PGE₁ was infused from completion of surgery until five minutes after tracheal extubation. Changes in heart rate (HR) and blood pressure (BP) were measured during and after tracheal extubation.

Results

In the control group, the HR, systolic BP, and diastolic BP increased during tracheal extubation. Administration of 0.1 μg · kg^?1 · min^?1 PGE₁ and 1 mg · kg^?1 lidocaine attenuated the increases in BP although 0.05μg · kg^?1 · min^?1 PGE₁ failed to do so. The inhibitory effect of the 0.1 μg · kg^?1 · min^?1 PGE₁ on BP was similar to that of lidocaine 1 mg · kg^?1 iv. The increase in HR was attenuated by lidocaine but not by PGE₁.

Conclusion

The intravenous infusion of 0.1 μg · kg^?1 · min^?1 PGE₁ given during emergence from anaesthesia and tracheal extubation is a useful method for attenuating the hypertension associated with noxious stimuli during this period.     

Inhibition of cerebral metabolic and circulatory responses to nitrous oxide by 6-hydroxydopamine in dogs

Purpose

To determine whether cerebral metabolic and circulatory consequences of N₂O result from activation of the sympathoadrenal system. The effects of pretreatment with intracistemal injection of 6-OHDA, which produces chemical sympathectomy, were studied in dogs.

Method

Seven days before measurement dogs were pretreated with intracisternal injection of either saline vehicle (sham-group) or 100 μg· kg^?1 6-hydroxydopamine (6-OHDA group). Cerebral blood flow (CBF) was measured using an electromagnetic flow-meter probe and cerebral metabolic rate for oxygen (CMRO₂) was calculated as the product of CBF and arterial-sagittal sinus blood oxygen content difference [C(a-v)O₂].

Results

In the sham group, N₂O (60%) increased CMRO₂ from 6.11 ± 0.21 ml· 100 g^?1· min^?1 to 7.10 ± 0.39 ml· 100g^?1· min^?1 and CBF from 63 ± 5 ml· 100 g^?1 · min^?1 to 173 ± 26 ml· 100 g^?1· min^?1. In the 6-OHDA group, CMRO₂ did not change during N₂O exposure, whereas CBF increased from 61 ± 3 ml· 100 g^?1· min^?1 to 135 ±19 ml· 100 g^?1· min^?1 but less then in the sham group. The 6-OHDA group displayed a reduction in cortical noradrenaline (NA) concentration from 263.2 ± 35.6 ng·g^?1 to 102.7 ± 16.5 ng· g^?1. Cortical dopamine (DA) concentration was not affected by 6-OHDA administration.

Conclusion

These results suggest that most of the increase in CMRO₂ and, at least a part of, the increase in CBF during N₂O exposure in the sham-group are related to sympathoadrenal-stimulating effects of N₂O.     

Nicardipine to control mean arterial pressure during extracorporeal membrane oxygenation

The authors present the use of nicardipine to control mean arterial pressure (MAP) in a 19–month-old boy who required venoarterial extracorporeal membrane oxygenation for 11 days for treatment of hydrocarbon aspiration. Nicardipine is an intravenously administered dihydropyridine calcium channel antagonist whose primary physiological action includes vasodilatation. Unlike other calcium channel blockers, it has limited effects on the inotropic and dromotropic function of the myocardium. Nicardipine was started at 5 μg·kg^?1·min^?1 and within five min lowered the MAP from a maximum value of 108 mmHg back to the baseline range of 60 to 80 mmHg. Once the MAP had returned to baseline values, infusion requirements varied from 1 to 3 μg·kg^?1·min^?1 to maintain the MAP at 60 to 80 mmHg during the 11 days of ECMO. No increase in dose requirements were noted during the 11 days.     

Effects of dexmedetomidine on propofol and remifentanil infusion rates during total intravenous anesthesia for spine surgery in adolescents

Introduction: Total intravenous anesthesia with propofol and a synthetic opioid is a frequently chosen anesthetic technique for posterior spinal fusion. Despite its utility, adverse effects may occur with high or prolonged propofol dosing regimens including delayed awakening. The current study investigated the propofol‐sparing effects of the concomitant administration of the α₂‐adrenergic agonist, dexmedetomidine, during spinal fusion surgery in adolescents. Methods: The surgical database of the department of orthopedic surgery was searched and patients (12–21 years of age) were identified who had undergone spinal fusion for either idiopathic or neuromuscular scoliosis during the past 24 months. Patients were assigned to two groups. Group 1 included patients anesthetized with propofol and remifentanil and group 2 included patients anesthetized with dexmedetomidine, propofol, and remifentanil. In the latter group, dexmedetomidine was administered as a continuous infusion of 0.5 μg·kg^?1·h^?1 started after the induction of anesthesia without a loading dose. Propofol was adjusted to maintain the bispectral index (BIS) number at 40–50 and remifentanil was adjusted to maintain the mean arterial pressure (MAP) at 50–65 mmHg. Labetolol or hydralazine was used if the MAP could not be maintained at 50–65 mmHg with remifentanil up to a maximum dose of 0.6 μg/kg/min. Statistical analysis included a nonpaired t‐test for parametric data (age, weight, remifentanil/propofol infusion requirements, and heart rate/blood pressure values). A nonparametric statistical analysis (Dunn) was used to compare BIS numbers. Parametric data are presented as the mean ± sd while nonparametric data are presented as the median and the 95th percentile confidence intervals. Results: Twelve patients received propofol–remifentanil–dexmedetomidine and 24 received propofol–remifentanil. There were no differences in the demographic data, BIS numbers or hemodynamic parameters between the two groups. There was a reduction in the propofol infusion requirements in patients who also received dexmedetomidine (71 ± 11 μg·kg^?1·min^?1) compared with those receiving only propofol–remifentanil (101 ± 33 μg·kg^?1·min^?1, P = 0.0045). No difference was noted in the remifentanil infusion requirements or the use of supplemental agents (hydralazine and labetolol) to maintain controlled hypotension. Conclusion: The concomitant use of dexmedetomidine in patients undergoing spinal fusion reduces propofol infusion requirements when compared with those patients receiving only propofol and remifentanil.