bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transfer of clonidine and dexmedetomidine across the isolated perfused human placenta
Authors: ALA‐KOKKO T. I. , PIENIMÄKI P. , LAMPELA E. , HOLLMÉN A. I. , PELKONEN O. , VÄHÄKANGAS K. 
Published: January 2009

Background: The placental transfer of the a2 receptor agonist clonidine, earlier used as an adjuvant in obstetric epidural analgesia, was compared with the transfer of the newer and more %‐selective agonist dexmedetomidine.Methods: Term placentas were obtained immediately after delivery with maternal consent and a 2‐hour recycling perfusion of a single placental cotyledon was performed. Disappearance from the maternal circulation, accumulation in placental tissue and appearance in the fetal circulation of clonidine or dexmedetomidine with the reference compound antipyrine were followed in 4 experiments for both drugs.Results: At 2 hours the percent dexmedetomidine found in the fetal circulation was 12.5 (SD 5.1)%, while 48.1 (SD 20.3)% was found in the perfused placental cotyledon. A higher mean clonidine than dexmedetomidine concentration was achieved in the fetal circulation (1.90 vs. 0.56 nmol/l, P <0.05). At 2 hours the percent clonidine found in the fetal circulation was 22.1 (SD 2.4)% (P <0.05), while 11.3 (SD 3.3)% (P <0.05) was re tained in the perfused placental cotyledon. The transfer indexes, describing maternal‐to‐fetal transfer of dexmedetomidine and clonidine normalized with the transfer of antipyrine, were 0.88 (SD 0.07) and 1.04 (SD 0.08) respectively (P <0.05).Conclusions: Dexmedetomidine disappeared faster than clonidine from the maternal circulation, while even less dexmedetomidine was transported into the fetal circulation. This was due to its greater placental tissue retention, the basis for which probably is the higher lipophilicity of dexmedetomidine.
Intravenous regional analgesia using morphine. The effect on postoperative pain following total knee arthroplasty
Authors: MCSWINEY M. , COOPER J. , CAMPBELL M. 
Published: January 2009

Background: We hypothesised that any peripheral action of morphine may contibute to improved postoperative analgesia. The aim of this study was to evaluate the analgesic efficacy of morphine administered preoperatively into an exsanguinated limb prior to total knee arthroplasty.Methods: A randomised, double‐blind, controlled study was performed in 50 patients having total knee arthroplasty surgery. Patients were divided into two groups. In the study group, 0.125 mg/kg morphine in 60 ml of saline was administered intravenously (iv) into the exsanguinated operative limb via a can‐nula in the foot. A saline intramuscular (im) injection was administered into the opposite leg. The control group received 60 ml saline iv into the operative leg and 0.12 5mg/kg morphine im into the opposite leg. Pain was assessed postoperatively using a 10‐point visual analogue scale and by comparing morphine requirements and demand: delivery ratios from a patient‐controlled analgesic pump.Results: We found no statistically significant difference between the groups in relation to any of the analgesic measures employed.Conclusions: Intravenous regional analgesia using morphine provides no analgesic advantage over the intramuscular route from 6–24 h postoperatively.
Recovery and outcome after propofol and isoflurane anesthesia in patients undergoing laparoscopic hysterectomy
Authors: NELSKYLÄ K. , ERIKSSON H. , SOIKKELI A. , KORTTILA K. 
Published: January 2009

Background: Laparoscopic hysterectomy (LH) is expected to provide fast and comfortable recovery, plus an early return to normal daily activities. This study was carried out to compare the outcome after LH in patients anesthetized with isoflurane or propofol.Methods: Sixty‐two patients undergoing LH were randomized to receive either isoflurane‐N2O or propofol‐N2O anesthesia. The times when the patients could drink, void and walk were recorded. Recovery was also evaluated by the Digit Symbol Substitution Test in the postanesthesia care unit (PACU) 60 and 120 min after the operation. The patients were also given a questionnaire on their further recovery (return to daily activities, pain and nausea) to be filled out at home.Results: Early recovery was significantly (P<.05) faster in the isoflurane group (eye opening within 3 min, orientation in 6 min) when compared to the propofol group (eye opening within 7 min, orientation in 14 min), but there was no significant difference in the other parameters of recovery. Most of the patients were discharged from the hospital on the first postoperative day in both groups. Twenty‐five percent of the patients, however, stayed two nights in hospital, mainly for social reasons. No difference was found regarding the recovery at home: the patients resumed their normal daily activities on about the sixth postoperative day (median).Conclusions: It is concluded that both isoflurane and propofol are suitable anesthetics for LH. In this study recovery was not fast enough to make the patients suitable for same‐day surgery.
Alleviation of the peripheral hemodynamic effects of dexmedetomidine by the calcium channel blocker isradipine
Authors: ROEKAERTS P. M. H. J. , LAWRENCE C. J. , PRINZEN F. W. , LANGE S. DE 
Published: January 2009

Background:Alpha2‐adrenergic agonists have peripheral vaso‐constrictive effects and central sympatholytic and sedative effects. Whereas the latter are the basis of their use in anesthesia, the former could limit their clinical application.Methods:To study whether a vasodilator could alleviate the systemic and coronary vasoconstrictor effects of dexmedetomidine without influencing the central sympatholytic effects, the calcium channel blocker isradipine was infused after a high dose of dexmedetomidine in anesthetized dogs.Results:Dexmedetomidine 10 μg. kg‐1decreased plasma concentrations of norepinephrine and epinephrine by more than 90“/0, heart rate by 39%, cardiac output by 647%, dp/dtmaxby 29% and increased mean arterial pressure by 55% and the left ventricular end‐diastolic pressure (LVEDP) 4‐fold as compared to baseline. In addition, coronary blood flow decreased by 52% and coronary venous oxygen saturation by 51%. Isradipine could completely antagonize all the coronary and systemic hernodynamic changes induced by dexmedetomidine, but only partially he increase in LVEDP. Isradipine caused no changes in plasma catecholamine levels.Conclusion:Isradipine could alleviate the peripheral hemodynamic actions of dexmedetomidine while having no effect on its central sympatholytic properties.
Low‐dose intravenous clonidine in children: plasma concentrations and haemodynamic response
Authors: BERGENDAHL H. T. G. , EKSBORG S. , LÖNNQVIST P. A. 
Published: January 2009

The beneficial perioperative effects of the alpha‐2 agonist clonidine have recently been verified in paediatric patients, and the pharmacokinetics have been found to be similar to what has been reported in adults. In a previous study we found that 2.5 μg/kg of clonidine causes a significant reduction in blood pressure. The aim of the present study was to evaluate if even lower doses of clonidine are associated with dose dependent or plasma‐dependent haemodynamic changes. In a prospective, single, blind, controlled clinical trial, 24 paediatric patients (age range: 13–78 months) were randomised into three groups: control, intravenous clonidine 0.625 μg/kg and intravenous clonidine 1.25 μg/kg respectively. Non‐invasive blood pressure and heart rate were recorded at 3‐min intervals for 30 min. Plasma concentrations of clonidine were analysed at 15 and 30 min post‐injection.A decrease in MABP compared to baseline values was observed in all groups. A significantly greater reduction in blood pressure was seen in all groups receiving clonidine compared to control.In conclusion, low doses of clonidine (0.625 and 1.25 μg/kg) were found capable of causing a blood pressure reduction compared to control. We could not establish a plasma concentration dependent blood pressure effect. The observed blood pressure reductions caused by clonidine were of moderate magnitude. No effect on heart rate was observed, a finding which most likely is explained by the inclusion of atropine in the premedication.
Inhaled nitric oxide does not prevent endotoxin‐induced lung injury in rabbits2
Authors: NISHINA K. , MIKAWA K. , TAKAO Y. , OBARA H. 
Published: January 2009

Background:Neutrophils, platelets, and cytokines are thought to play a pivotal role in the pathogenesis of endotoxin‐induced lung injury which resembles features of acute respiratory distress syndrome (ARDS). For initiation of this pathological process, neutrophils and platelets are activated and adhere to pulmonary endothelium. Nitric oxide (NO) inhibits adhesion and activation of these cells and decreases the cytokine level in bronchoalveolar lavage (BAL) fluid obtained from patients with ARDS. Limited data are available on the effect of NO treatment before and after endotoxin on the development and advance of ARDS. The aim of the current study was to determine whether NO inhalation prevents acute lung injury.Methods:Thirty‐two male anaesthetized rabbits were randomly assigned to receive one of four treatments (n=8 each); Group S‐N received saline with nitrogen (N2), Group S‐NO received saline infusion with NO (20 p.p.m.) inhalation, Group E‐N received an infusion ofEscherichia coliendotoxin 100 μg/ kg over 60 min with inhalation of N2, and Group E‐NO received endotoxin with NO (20 p.p.m.) inhalation. The lungs of the rabbits were ventilated with 40% oxygen until 6 h after the start of endotoxin or saline administration. Haemodynamics and PaO2were recorded during the ventilation period. After observation, the lung wet‐to dry‐(W/D) weight ratio, lung mechanics, and. cell fraction, activated complements, cytokines, arachidonic acid metabolites, and albumin concentrations in the BAL fluid were measured and analysed. Light microscopic findings were compared among the four groups.Results:Pulmonary hypertension and deterioration of oxy‐genation by endotoxin were less pronounced in rabbits receiving NO. The lung compliance after endotoxin was similar in Groups E‐NO and E‐N. The W/D weight ratio and neutrophils and albumin concentrations in the BAL fluid increased in Groups E‐NO and E‐N. The BAL fluid concentrations of interleukin‐8, thromboxane A2, and prostacyclin were similar in the two endotoxin‐treated groups. Endotoxin caused extensive morphologic lung damage regardless of NO inhalation.Conclusions:The increase in pulmonary arterial pressure and deterioration of oxygenation were less in endotoxin‐exposed rabbits receiving NO inhalation compared with those receiving N2. Accumulation of neutrophils and platelets in the lung, morphological lung damage, and the release of cytokines and prostanoids were observed in the E‐NO group. However, we are unable to extrapolate these results directly to the human clinical setting because of the short observation period, the use of only one dose of NO, and the species difference.
Synthetic 8‐ornithine‐vasopressin, a clinically used vasoconstrictor, causes cardiac effects mainly via changes in coronary flow
Authors: GRAF B. M. , FISCHER B. , STOWE D. F. , BOSNJAK Z. J. , MARTIN E. O. 
Published: January 2009

Background:8‐ornithine‐vasopressin (ornipressin, POR‐8®) is used as a potent peripheral vasoconstrictor mainly in combination with local anaesthetics. Because omipressin causes vasoconstriction, any myocardial depressive effects could be caused indirectly by reduced myocardial perfusion secondary to coronary vasoconstriction, or directly by effects on myocardial tissue.Methods:On isolated guinea pig hearts, we compared direct effects of ornipressin by perfusion at constant flow with indirect effects by perfusion at constant pressure by Langendorff technique. Ornipressin concentrations tested were 0.05, 0.1, 0.25, 0.5 and 1.0 IU/L (1 International Unit (IU) omipres‐sin=2.8 μg)Results:Coronary flow decreased significantly (P<0.001) in concentration‐dependent manner with ornipressin at constant pressure while AV conduction time and percentage O2extraction (%O2E) increased and heart rate (HR), systolic left ventricular pressure (LVP) and myocardial O2consumption (MVO2) decreased. Coronary perfusion pressure increased significantly with increasing omipressin at constant coronary flow while HR and AV time were unchanged and LVP decreased only at the higher concentrations. At an identical or slightly reduced HR‐LVP product (RPP), MVO2increased up to 27±6% at 1.0 IU/L omipressin during constant flow perfusion.Conclusion:An increase in %O2E coupled with a decrease in coronary flow at constant pressure is consistent with myocardial depression secondary to reduced tissue perfusion. These omipressin‐induced effects are not evident at constant coronary flow except for a small but direct myocardial depressant effect on LVP at higher concentrations. The increase of MVO2at constant flow, despite equal or even reduced work, is described as Gregg's phenomenon and it is probably due to an increase in coronary perfusion pressure during coronary vasoconstriction. Even though extrapolation of our results in humans is questionable, the current indication for use of ornipressin as vasoconstrictor may need to be reconsidered, especially in patients with reduced coronary reserve.
Four years' treatment with ketamine and a trial of dextromethorphan in a patient with severe post‐herpetic neuralgia
Authors: KLEPSTAD P. , BORCHGREVINK P. C. 
Published: January 2009

N‐methyl‐D‐aspartat (NMDA) receptors are involved in the development of neuropathic pain. Ketamine, a non‐competitive NMDA receptor antagonist, has in several case reports given pain relief but efficacy in dosages tolerated in long‐term ketamine treatment is unknown. Another substance with an antagonist action at NMDA receptors and which is approved for per‐oral administration is dextromethorphan. In a randomized study dextromethorphan was no better than placebo for neuropathic pain but this does not exclude efficacy in selected patients.We report a patient with severe post‐herpetic pain resistant to conventional pain treatment which was treated with ketamine for 4 years with good pain relief. The practical application of long‐term treatment in different administration forms of ketamine is described. The patient also responded with pain relief in a double‐blind trial with oral dextromethorphan.
Peripheral neurologic deficits in relation to subarachnoid or epidural administration of local anesthetics for surgery
Authors: PLEYM H. , SPIGSET O. 
Published: January 2009

Background: Recent case reports have suggested that subarachnoid or epidural administration of local anesthetics may cause peripheral neurologic deficits.Methods:To describe the course and evaluate possible risk factors of such reactions, 21 reports in the Swedish adverse drug reactions register were reviewed.Results: The reports concerned subarachnoid administration of hyperbaric lidocaine (n=9), plain bupivacaine (n=4), hyperbaric bupivacaine (n=2), bupivacaine with epinephrine (n=1) and mepivacaine (n=l), and epidural administration of bupivacaine (n=2) and mepivacaine (n=2).Pain in the lower extremities was reported in 12 patients (57%)and paresthesias/hypesthesias were reported in 11 patients (52%). Seven reports (33%)concerned low back pain or abdominal pain from Th9‐ThlO and downwards. Urinary incontinence was reported in 3 patients, fecal incontinence in 2 patients, and erectile dysfunction, loss of sensation of full bladder and quadriceps muscle paresis were each reported in one patient. Two clinically distinct subgroups of patients were identified, one group with reversible nerve root affection which disappeared within 2 weeks and one group with apparently irreversible nerve root affection, still persistent after 1 month to 4 years. h the group with reversible root symptoms, none had motor deficits, whereas 50% had motor deficits in the group with irreversible symptoms. Possible risk factors include concomitant peripheral neurologic disease and use of other drugs associated with neurotoxicity.Conclusion: This database study does not contain complete information for the cases reported, and a causal relationship between subarachnoid or epidural administration of local anesthetics and neurologic deficits therefore remains uncertain. The increase in the number of reports on lidocaine after the introduction of very fine‐bore spinal needles is consistent with the suspicion that lidocaine at the concentration 50 mg/ml is neuro‐toxic and that it may not be diluted rapidly enough in the cere‐brospinal fluid when injected through such needles.
Comparison of continuous epidural infusion of fentanyl and bupivacaine with intermittent epidural administration of morphine for postoperative pain management in children
Authors: KART T. , WALTHER‐LARSEN S. , SVEJBORG T. F. , FEILBERC V. , ERIKSEN K. , RASMUSSEN M. 
Published: January 2009

Background: The aim of this study was to compare epidural infusion of bupivacaine and fentanyl and intermittent epidural morphine with regard to analgesic effect, and incidence and severity of side effects in children undergoing major abdominal or genito‐urological surgery in order to improve the postoperative pain management of children.Methods:A double‐blind, block‐randomised study design was used. Thirty‐one children aged 3 months to 6 years undergoing major abdominal or genito‐urological surgery were studied. After induction of anaesthesia a lumbar epidural catheter was placed at L3–4 or L4–5. Postoperatively, the children received either 30 μg/kg of morphine every 8 h or a continuous infusion of fentanyl 2 μg/ml and bupivacaine 1.0 mg/ml at a rate of 0.25 ml.kg‐1.h‐1. All children additionally received rectal paracetamol in doses of 50–100 mg.kg‐1. d‐1 on a regular basis, and if necessary supplementary intravenous morphine in doses of 50 μg/kg. Postoperatively, pain, administration of supplemental morphine and side effects were recorded 5 times by one observer during the day of surgery and the first postoperative day. All children had an epidural catheter throughout the study period.Results: Both regimens provided effective analgesia, but significantly better pain relief was obtained in children receiving the fentanyl/bupivacaine regimen. Sedation, pruritus, vomiting, and administration of antiemetics were seen in both treatment groups, and even though both the incidence and severity of side effects tended to be higher in children receiving morphine, no statistically significant difference was found. No episodes of respiratory depression or motor blockade were noticed.Conclusion: Continuous epidural infusion of fentanyl and bupivacaine was found to be superior to intermittent epidural morphine. The initial regimen should be fentanyl 2 μg/ml and bupivacaine 1.0 mg/ml infused at a rate of 0.25 ml. kg‐1. h‐1.
Haemodynamics during inhalation of a 50% nitrous‐oxide‐in‐oxygen mixture with and without hypovolaemia
Authors: HAHN R. G. , RIDDEZ L. , BRISMAR B. , STRANDBERG Å. , HEDENSTIERNA G. 
Published: January 2009

Background: Inhalation of a gas mixture containing 50% nitrous oxide in oxygen (N2O/O2) is widely used for pain relief in emergency situations, which may also be associated with blood loss. The aim of this study was to evaluate the haemodynamic effects of this gas mixture in normo‐ and hypovolaemic subjects.Methods: Six healthy males were studied during inhalation of N2O/O2 before and after withdrawal of 900 ml of blood. On each occasion, we measured systemic and pulmonary arterial pressures, cardiac output, blood gases, extravascular lung water, and the blood flow and oxygen consumption in the whole body, liver and kidneys.Results: Inhalation of N2O/O2 reduced the stroke volume and increased peripheral resistance. Oxygen uptake decreased in the liver (‐30%) and in the whole body (‐23%). Blood withdrawal reduced the pulmonary arterial and central venous pressures (‐30 to ‐50%) and further decreased stroke volume and the blood flows to the liver and the kidney (‐15%). The extravascular lung water tended to increase both during inhalation of N2O/O2 and during hypovolaemia.Conclusion: N2O/O2 aggravated the hypokinetic circulation induced by hypovolaemia. However, the oxygen consumption decreased only during inhalation of N2O/O2. This opens up the possibility that the cardiodepression associated with N2O/O2 is caused by a change in metabolic demands.
Outcome effects of different protective hypothermia levels during cardiac arrest in rats
Authors: YLI‐HANKALA A. , JR H. L. EDMONDS , JIANG Y. D. , HIGHAM H. E. , ZHANG P. Y. 
Published: January 2009

Background: Although hypothermia is widely used to protect the brain during cardiac and neurologic surgery, the optimal level of cooling has not been established. This study examined the protective effect of graded levels of surface cooling on cerebral function in rats after complete global cerebral ischemia.Methods: Groups of ketamine‐anesthetized rats (13 animals in each group) were cooled to cranial temperatures of 34, 30, 27, 24, or 22 °C before circulatory arrest. Also a normothermic (37°C) group was tested. After cooling, an 11‐min circulatory arrest was produced by atraumatic chest compression. Circulatory arrest was followed by cardiopulmonary resuscitation and rewarming without postischemic intensive care. On the fifth postinsult day, neurologic outcome was scored on a 50‐point neurodeficit scale (NDS O=normal). The percent of ischemic pyramidal neurons in the CAI hippocampal region was also determined.Results: There were no survivors in the normothermic group. Neurologic recovery was enhanced with 30°C cranial temperature, as compared to outcome in the 34°C group. Further cooling did not change outcome. The neurodeficit scales were significantly lower in all other groups compared to the 34°C group on the fifth postinsult day. The percent of ischemic neurons did not change significantly as a function of cooling, but the lowest count appeared at 27°C.Conclusion: In this model, moderate (30°C) cooling improved neurologic outcome. There was no additional benefit from more extreme hypothermia.
Inhibitory effect of local anaesthetics on reactive oxygen species production by human neutrophils
Authors: MIKAWA K. , AKAMATSU H. , NISHINA K. , SHIGA M. , MAEKAWA N. , NIWA Y. 
Published: January 2009

Background:Reactive oxygen species (ROS) generated from neutrophils accumulated in various major organs are thought to play a pivotal role in the pathogenesis of host auto‐injury. Lidocaine has been shown to reduce the injury. We investigated the effect of local anaesthetics (lidocaine, mepivacaine and bupivacaine) on ROS production by neutrophils using anin vitrosystem.Methods:We measured the production of superoxide (ferric‐ytochrome c method), hydrogen peroxide (H2O2: scopoletin fluorescence technique), and hydroxyl radical (OH.: ethylene gas method) by neutrophils isolated from human adult volunteers in the absence and presence of lidocaine (2–200 μg/mL), mepivacaine (3–300 μg/mL), and bupivacaine (3–300 μg/mL). We also measured the ROS generation in acell‐free(xanthinexanthine oxidase) system.Results:Lidocaine and mepivacaine at higher levels significantly decreased the production of ROS by neutrophils. However, these local anaesthetics at clinically relevant blood concentrations had no effect on the levels of ROS. Furthermore, lidocaine and mepivacaine failed to reduce ROS generated by thecell‐freesystem. Bupivacaine did not decrease ROS generation by either generating system.Conclusion:In conclusion, in the presentin vitrosystem, only concentrations of lidocaine and mepivacaine 100‐fold higher than clinically feasible ones reduced ROS production by human neutrophils. However, the local anaesthetics at clinically relevant blood concentrations had no suppressive effect. Further studies usingin vivosystems are required to elucidate the inhibitory effects of local anaesthetics on ROS generation in clinical settings.