bluuebunny/crossref_metadata_2025 huggingface dataset:
Opioids in the brain: supraspinal mechanisms in pain control
Authors: JENSEN T. S.
Published: January 2009

Systemically administered opioids produce a profound inhibition of noxious‐evoked activity peripherally, spinally and supraspinally in several species, including man. The role of the brain in opioid mediated‐pain control has been less well characterized than that occurring at lower levels in the nervous system. Yet, classical studies indicate that in morphine‐induced analgesia the individual senses noxious stimuli, but the affective, motivational and aversive character of the stimulus is no longer present. This observation indicates that morphine probably exerts a specific action on those brain systems that control complex behaviors like aversion and motivation. The failure to document such effects in experimental studies may in part be explained by less suitable methods for assessing antinocicep‐tion, e.g. measurements of simple reflex behaviors. Experimental animal studies show that supraspinal opioids may influence nociception by several distinct mechanisms, which differ from those seen in the spinal cord:

 Change of activity in descending bulbospinal pathways.

 Direct inhibition of noxious throughput at brainstem level.

 Indirect inhibition of noxious responding brainstem neurons projecting to supraspinal centers.

 Influence ascending forebrain systems.

 Direct cortical or thalamic inhibition.

In humans, the antinociceptive actions of opioids occurring in the brain has until recently been like looking into a “black box”. The introduction of new imaging techniques may provide new tools for directly measuring the antinociceptive action of opioids in the brain under normal and pathological conditions. In particular, the emotional‐affective aspect of pain and how this is modulated by opioids will be of interest to study.
Cancer pain classification
Authors: TWYCROSS R.
Published: January 2009

About three quarters of patients with advanced cancer experience pain. Most of these have multiple pains. Causes of pain fall into four broad categories: the cancer itself, related to the cancer +/‐ debility, related to treatment, concurrent disorder. From a neuropathological perspective, pain is either nociceptive or neuropathic. This distinction is important because neuropathic pain is generally less responsive to analgesics than nociceptive pain. Recognition of functional muscle pain is important. Patients with severe chronic pain do not necessarily look in pain because of the absence of autonomic concomitants. Whatever the cause, pain is a ‘somatopsychic’ experience.
Psychomotor and cognitive functioning in cancer patients
Authors: SJOGREN P.
Published: January 2009

Psychomotor and cognitive dysfunction in cancer patients can be classified into two main categories according to etiology: disease‐induced factors (metabolic disturbances, brain metastasis, pain, etc.) and treatment‐related factors (drugs, antineoplastic therapy, etc.). In particular, the effects of chronic opioid administration in cancer patients have been subjected to investigations, and most studies have been engaged in assessment and treatment of the cerebral dysfunction. Early studies found that cancer patients in chronic oral opioid therapy had prolonged continuous reaction times, and that the opioids seemed to be mainly responsible for the prolongation. Significant dose escalations of opioids (≥ 30%) caused transiently impaired psychomotor and cognitive functions in cancer patients. Cancer patients in chronic oral opioid therapy did not achieve any advantages changing to epidural opioid therapy with regard to faster continuous reaction times and less pain.

Large doses of opioids are often required to control severe pain in cancer patients. As increased sedation and impaired psychomotor and cognitive functions often occur, a number of studies have investigated the use of amphetamine derivatives to counteract the sedative side‐effects of opioid. These drugs seem promising during high‐dose opioid therapy and their use may be particularly rewarding in poor opioid‐responsive pain conditions such as incident and neuropathic pain.
Effects of dihydroergotamine and sumatriptan on isolated human cerebral and peripheral arteries and veins
Authors: NILSSON F. , NILSSON T. , EDVINSSON L. , BJÖRKMAN S. , NORDSTRÖM C.–H.
Published: January 2009

Background: Pharmacological cerebral vasoconstriction has recently been suggested as treatment for patients with increased intracranial pressure (ICP) after severe traumatic brain lesions. Hypothetically, a moderate constriction of precapillary resistance vessels might be advantageous since it decreases intracapillary blood pressure, and a contraction of cerebral veins might effectively reduce intracranial blood volume and ICP. This report examines thein vitroeffects of two vasoconstrictors, dihydroergotamine (DHE) and sumatriptan, which may be considered for treatment of increased ICP.

Methods: The reactivity of isolated small human cerebral, subcutaneous and omental arteries and veins were studied during exposure to different concentrations of DHE and sumatriptan.

Results: Both sumatriptan and DHE induced concentration–dependent contractions in human cerebral arteries and veins and 50% of maximum contractions were obtained at significantly lower concentrations of DHE than of sumatriptan. The maximum contraction of cerebral arteries was significantly higher with sumatriptan than with DHE. Both drugs caused contractions of subcutaneous arteries at concentrations of 10‐7–10‐6M, which is within the therapeutic concentration range of sumatriptan, while no effect was obtained in omental vessels.

Conclusions: Both DHE and sumatriptan cause contraction of isolated human cortical arteries and veins at very low concentrations. The differences observed between the two drugs may be explained by the fact that DHE is an α–adrenergic as well as a 5–HT agonist while sumatriptan acts specifically on 5–HT receptors. The study supports the hypothesis underlying the use of DHE for the treatment of increased ICP in patients with severe traumatic brain lesions.
Spinal, epidural or propofol anaesthesia for out–patient knee arthroscopy?
Authors: DAHL V. , GIERLØFF C. , OMLAND E. , RÆDER J. C.
Published: January 2009

Background: We have compared three different methods of anaesthesia for out–patient knee arthroscopy in terms of perioperative conditions, postoperative pain, time taken and economy.

Methods: 91 ASA I–II patients scheduled for elective knee arthroscopy were included. After premedication with diazepam 10 mg and naproxene 500 mg orally, they were randomly assigned into one of three groups: Group S (n=32) received spinal anaesthesia with lidocaine 50 mg/ml 1.5–2 ml in 7.5% glucose through a 27–G Quincke needle, Group E (n=29) received epidural anaesthesia with mepivacaine 20 mg/ml and epinephrine 5 μg/ml, 15–20 ml, and Group P (n=30) received propofol anaesthesia with a bolus induction of 2 mg/kg followed by infusion.

Results: The time from start of anaesthesia until start of operation was significantly less in Group P than in the two other Groups: 7.45.4 min as compared to 23.04.8 min in Group S and 31.09.1 min in Group E (meanSD, P<0.05). After end of surgery, the duration of the postoperative regional block was 7528 min in Group S and 125 79 min in Group E (P<0.05). In Group S and Group E the postoperative pain was significantly less than in Group P at admission to the recovery unit and 60, 120 and 180 min later (P<0.05). The overall incidence of postoperative nausea or vomiting was less than 5% with no differences between the groups. One patient in Group E had block failure and one patient in Group S had a post–spinal headache. The perioperative costs of drugs and disposables were highest in Group P (30 USD) and lowest in Group S (6.5 USD).

Conclusion: Propofol anaesthesia results in the shortest stay in the operation theatre but a higher degree of postoperative pain and a higher cost of drugs and disposables.
Intravenous induction of general anaesthesia with eltanolone in children 6–15 years of age
Authors: BESKOW A. , WERNER O. , WESTRIN P.
Published: January 2009

Background:Eltanolone is a short‐acting intravenous anaesthetic, formulated as an oil‐water emulsion. The aim of the present study was to estimate the anaesthetic dose (ED50) for induction in children 6–10 and 11–15 years of age and to collect safety data.

Methods:Forty‐nine unpremedicated children, all ASA I or II, divided in one pilot‐study group, with 5 children 6–15 years and two main study groups, 6–10 and 11–15 years of age, were studied. The first patient in each study group was given 0.86mg/kg of eltanolone iv over 20s. Fifty s after injection the chin was gently lifted to ‘the sniffing position’ and the anaesthesia mask was placed over the face. Induction was considered satisfactory if there was no gross movement, coughing or response to verbal command during the following 15s. The dose selected for the next patient was based on the observed response: if induction was not classified as satisfactory the dose was increased by a factor of 20%, otherwise it was decreased by the same factor. ED50was estimated as described by Dixon and Massey.

Results:In children 6–10 years of age ED50was 0.68 (0.49‐0.92; 95% confidence limits) mg/kg and in children 11–15 years of age 0.53 (0.41‐0.68) mg/kg. No child showed sign of pain on injection. One patient developed urticaria and 15 patients had transient rash after induction. Two patients (both responders receiving 0.86 and 0.40mg/kg respectively) had apnoea lasting more than 15 s. Involuntary movements occurred in one patient.

Conclusions:The ED50of eltanolone for induction of anaesthesia in unpremedicated children 6–10 years of age was 0.68 mg/kg and in children 11–15 years of age 0.53 mg/kg. The findings suggest that an induction dose for children 6–15 years of age of about l mg/kg would be adequate in most cases. No serious adverse events were recorded. However, the drug has subsequently been withdrawn from further investigation due to an unacceptable incidence of rash and urticaria.
Hepatic energy charge and adenine nucleotide status in rats anesthetized with halothane, isoflurane or enflurane
Authors: METS B. , JANICKI P. K. , JAMES M. F. M. , HICKMAN R.
Published: January 2009

Background:Volatile anesthetics are known to have varying effects on hepatic oxygen supplyin vivoand have been shown to depress hepatic mitochondrial respiration and so energy chargein vitro.However, the effect of halothane, isoflurane and enflurane on hepatic adenine nucleotide statusin viuohas not been evaluated.

Methods:Ninety male rats were exposed to 40% oxygen (n=22) or 40% oxygen in equipotent (1 MAC) concentrations of halothane (1%) (n=23), isoflurane (1.4%) (n=22) or enflurane (2%) (n=23) for 2 hours. All animals were then administered intraperitoneal pentobarbital and anesthesia continued and laparotomy was performed. A liver biopsy was taken for determination of hepatocellular adenosine‐5‐triphosphate (ATP), adenosine‐5‐diphosphate (ADP) and adenosine‐5‐monophosphate (AMP) and computation of energy charge (EC) from ((ATP+1/2 ADP)+(ATP+ADP+AMP)) and total ade nine nucleotides (TAN) from (ATP+ADP+AMP). After the biopsy the aorta was cannulated for blood sampling.

Results:Rats in each group were similar in weight, as well as acid base and blood gas status just after liver biopsy. Hepatic energy charge, ATP, ADP, AMP, and TAN levels were not different in animals receiving either halothane, isoflurane or enflurane when compared with those receiving only oxygen.

Conclusions:One MAC of anesthesia for a period of 2 hours with the described volatile anesthetic agents did not affect adenine nucleotide statusin viuoin rats.
Metoclopramide reduces the induction dose of propofol
Authors: PAGE V. J. , CHHIPA J. H.
Published: January 2009

Background:Metoclopramide has been shown to reduce the dose of thiopentone required for induction of anaesthesia. When propofol is used, there have been conflicting results with one small study showing a reduction in the anaesthetic dose and one study failing to demonstrate any effect.

Methods:Two groups of 30 patients were studied. The patients were randomised to receive either saline 0.03 ml/mg or metoclopramide 0.15 mg/kg 5 min before a manual injection of propofol at a set rate.

Results:This study shows a reduction in the dose of propofol required for the induction of general anaesthesia following an intravenous dose of metoclopramide. The induction dose of propofol was reduced by 24%.

Conclusions:The mechanism of reduction of propofol dose by metoclopramide is unknown; it may involve GABA or result from a more complex interaction involving dopamine blockade by metoclopramide.
Delayed elevation of plasma endothelin‐1 during unilateral alveolar hypoxia without systemic hypoxemia in humans
Authors: TAKEDA S. , NAKANISHI K. , INOUE T. , OGAWA R.
Published: January 2009

Background:The mechanisms by which acute alveolar hypoxia induces pulmonary vasoconstriction remain unclear. We investigated whether endothelin‐1 (ET‐1) could be detected in plasma during pulmonary alveolar hypoxia without systemic hypoxemia (one‐lung hypoxia) and whether the levels could be related to hemodynamic status in humans.

Methods: Thirteen adult patients with primary lung carcinoma were studied prior to surgery. Anesthesia was induced with fentanyl, diazepam, and pancuronium iv. Differential lung ventilation was performed for 40 min. The right lung was ventilated with a mixture of 6% O2, 5% CO2 and 89% N2 and the left lung ventilated with 100% O2. Blood gas values, hemodynamic parameters, and plasma ET‐1 levels were measured.

Results: Mean pulmonary artery pressure increased from 13.±3.5 to 17.·3.2mm Hg (P <0.01) after 20 min of one‐lung hypoxia. The plasma ET‐1 levels in arterial blood and wedged right pulmonary arterial blood increased from 1.69M.61 to 2.13 ±0.48 μg/ml (P <0.01) and from 1.75±.47 to 2.26±.40 μg/ ml (P <0.001), respectively, after 40 min of one‐lung hypoxia.

Conclusions: We concluded that ET‐1 may play a supporting, but not a primary, role in human hypoxic pulmonary vasoconstriction.
Myocardial cooling and right ventricular function in patients with right coronary artery disease: antegrade vs. retrograde cardioplegia
Authors: HONKONEN E. L. , KAUKINEN L. , PEHKONEN E. J. , KAUKINEN S.
Published: January 2009

Background: Protection of the right ventricular (RV) myocardium during ischaemia in cardiac surgery is difficult, especially in patients with severe right coronary artery (RCA) disease. Retrograde coronary sinus cardioplegia is thought to distribute uniformly, but doubts still remain as to its adequacy in RV preservation. This study evaluated distribution of antegrade vs. exclusively retrograde coronary sinus cold blood cardioplegia by assessing myocardial cooling and compared the effects on RV function.

Methods: Fifty‐eight patients scheduled for elective coronary artery surgery ‐ 29 patients with significant RCA disease and another 29 with no significant RCA stenosis (controls) ‐ were randomised to receive either antegrade or retrograde cold blood cardioplegia through either aortic root or conventional self‐inflating coronary sinus catheter (RCA‐ante, RCA‐retro, C‐ante and C‐retro groups). RV function was assessed by fast‐response thermodilution. Myocardial temperatures were measured in the anterior and posterior wall of the right and left ventricle.

Results: Cooling of the posterior wall of the RV was effective only in the control patients given antegrade cardioplegia (14.7°C), whereas in the other groups the lowest myocardial temperatures there remained above 20°C (RO.001). In patients with obstructed RCA both antegrade and retrograde cold cardioplegia led to uneven cooling of the myocardium. After cardiopulmonary bypass the RV ejection fraction (RVEF), RV stroke work index (RVSWI) and cardiac index (CI) were significantly reduced in the RCA‐retro group, and RVSWI and CI in the C‐retro group, too. Regression analysis showed an inverse relationship between the temperatures of the posterior walls of the ventricles and changes in the RVEF and CI.

Conclusions: Retrograde and antegrade cardioplegia alone were not effective in reducing the temperature of the posterior wall of the RV in the patients with obstructed RCA, in whom with retrograde cardioplegia RV haemodynamics were impaired for 1 hour following bypass. Neither retrograde nor antegrade cardioplegia alone can be relied on to protect the posterior wall of the RV in the patients with obstructed RCA.
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.
The cytokine response in a patient undergoing surgery for an ACTH‐producing tumor
Authors: HÖHNDORF K. , TOFT P. , TBNNESEN E.
Published: January 2009

The administration of glucocorticoids has been used to inhibit the cytokine production in patients undergoing cardiac surgery during cardiopulmonary bypass. In this case report the cytokine response in a 43‐year‐old man undergoing operation for an ACTH‐producing lung tumor is presented. There had been clinical symptoms for about 18 months and 8 months before operation elevated serum concentrations of ACTH and cortisol were measured. The patient underwent thoracotomy with removal of the tumor and the cytokine response in relation to surgery was measured as plasma concentrations of IL‐lα, IL‐6, TNFα and TNFβ. With the long‐lasting high endogenous glucocorticoid production low or undetectable cytokine levels were expected in this patient. However, a marked and prolonged IL‐6 and TNFβ response was measured while IL‐1α and TNFα were detectable in only a few samples. The cytokine response in this patient was different from the response normally found in patients undergoing major surgery.
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.
The use of indomethacin to treat acute rises of intracranial pressure and improve global cerebral perfusion in a child with head trauma
Authors: IMBERTI R. , BELLINZONA G. , ILARDI M. , BRUZZONE P. , PRICCA P.
Published: January 2009

Background: The use of vasoconstrictors (e.g. dihydroergotamine, indomethacin) for the treatment of increased intracranial pressure (ICP) secondary to brain trauma is controversial. In particular, it has been suggested that vasoconstrictors be employed only for intracranial hypertension secondary to hyperemia, when venous jugular bulb saturation (SjO2) is >75%. Method We administered indomethacin as a bolus i.v. (5–10 mg) on 18 occasions to a multiple‐injured 3‐year‐old child with acute rises of ICP secondary to severe brain trauma (GCS score 7) determining a large hypodensity area in and swelling of the right hemisphere.

Results: Before indomethacin administration the average of mean ICP was 68.1 ± 10.8 (SD) mm Hg (range 47–84) and the cerebral perfusion pressure (CCP) was 38.4±10.4 mm Hg (range 30–65). In response to indomethacin, ICP dropped in a few seconds to 22.7±5.6 and CCP increased to 82.4±6.1 mm Hg (P <0.001), while the mean arterial pressure remained unchanged. On 6 occasions SjO2 was also evaluated immediately before and 5 and 10 min after indomethacin administration. Before indomethacin administration, SjO2 values were within the normal range on 2 occasions and abnormally low on four. SjO2 increased from the mean value of 45.6215.7 to 59.828.9 (after 5 min) and 60.6212.4% (after 10 min) (P< 0.01 versus pre‐indomethacin). At the same time the cerebral venous pH increased from 7.4320.01 to 7.4550.01 (P=0.01). These findinge suggest that the global cerebral perfusion was improved. Eighteen days after injury the child was awake and was discharged from the ICU.

Conclusion: To our knowledge, increase of SjO, in response to indomethacin has not been previously reported. Although great caution is necessary in the use of indomethacin for the treatment of ICE these findings suggest that indomethacin can be useful for the treatment of acute rises of ICP compromising severely the CCP, even if SjO, is normal or abnormally low. Under these circumstances, indomethacin can improve the global cerebral perfusion.
National survey on the anaesthetist's beliefs, opinions, behaviour and techniques in postoperative pain control in Italy
Authors: NOLLI M. , APOLONE G. , NICOSIA F.
Published: January 2009

Background: Using a personal, anonymous questionnaire developed ad hoc, we tried to document the role, the problems and the activities of Italian anaesthetists in postoperative pain control.

Methods: A random selection ‐ stratified by region ‐ was made from a list of 971 hospitals. The final sample was made up of 395 departments of anaesthesia and intensive care from 369 hospitals. The completeness and consistency of each questionnaire were assessed.

Results: The response rate achieved was 78.9% (312 centres in 293 hospitals) with 2435 evaluable questionnaires corresponding to 30% of all Italian anaesthesia departments and 25% of Italian anaesthetists. Only 15.2% of anaesthetists are completely responsible for the postoperative analgesia (POA) (prescriptions and evaluations) and an established attitude for POA (protocols/guidelines) exists in 18 departments only. 60% of anaesthetists use routinely the intramuscular route, 55.2% the intravenous route (infusion plus bolus), and 23.7% the spinal/epi‐dural route. Only 6.2% of the anaesthetists use the patient‐controlled analgesia system. Nonsteroidal anti‐inflammatory drugs (NSAIDs) are the most commonly used agents (47% NSAID vs 37.9“/0 opioids; NSAID‐opioid association 14.7%). A local anesthetics‐opioids association is preferred for the spinal/ epidural route (15.1%) only (local anaesthetic 4.9% only; opioids alone 2.7%). Lack of time, work organization, technique knowledge/training, trust in nursing‐ward staff, difficulty in monitoring the patient on the ward, concern about opioid use leading to ventilatory depression, and administration errors are reported to be the main factors that limit an appropriate approach to postoperative pain (POP), the correct use of analgesics and a free choice of POA technique.

Conclusion: This survey shows that Italian anaesthetists do not consider the postoperative period to be their own personal work area and that POA is to be considered as a matter of individual choice.
Elastic work of breathing during continuous positive airway pressure in intubated patients with chronic obstructive pulmonary disease (theoretical analysis and experimental validation)
Authors: AERTS J. G. J. V. , BERG B. VAN DEN , VERBRAAK A. F. M. , BOGAARD J. M.
Published: January 2009

Background: Continuous positive airway pressure (CPAP) is known to decrease inspiratory work of breathing in patients with chronic obstructive pulmonary disease (COPD). This effect is primarily attributed to a reduction in inspiratory elastic work of breathing (Wi,el) related to a decrease in intrinsic positive end‐expiratory pressure (PEEP).

Methods: The aim of this study is to design a model for computation of Wi,el on the basis of respiratory mechanics in patients with COPD, at various intrinsic PEEP‐ and CPAP‐levels. The model was used to estimate the optimal CPAP‐level with respect to the intrinsic PEEP‐level in terms of reduction of Wi,el. Calculations of the decrease in Wi,el due to CPAP obtained with the model were compared to changes in Wi,el and total work of breathing (Wi,tot) determined from respiratory measurements in patients with COPD.

Results: Model calculations revealed that Wi,el was minimal whenever a CPAP‐level equal to the intrinsic PEEP‐level was applied. When a CPAP‐level exceeding the intrinsic PEEP‐level was applied, the reduction in Wi,el was less. Comparing these results to the respiratory measurements, a similar pattern in reduction of Wi,el and Wi,tot was established, although absolute values of the differences were smaller in the experimental data.

Conclusion: This study indicates that in order to reduce Wi, el in patients with COPD, intrinsic PEEP should be measured and the CPAP‐level adjusted to the intrinsic PEEP‐level.
Propofol induces a lowering of free cytosolic calcium in myocardial cells
Authors: Lr Y.‐C. , RIDEFELT P. , WIKLUND L. , BJERNEROTH G.
Published: January 2009

Background:The intravenous anaesthetic drug propofol has been shown to depress myocardial contractility. Ketamine, on the other hand, is a well‐documented cardiovascular stimulant. These differences could possibly be due to different effects of the drugs on the calcium homeostasis of the myocardium. Methods: The fluorescent intracellular probe fura‐2 acetoxyme‐thy1 ester (fura‐2/AM) was used in thisin vitroinvestigation to study the influence of intravenous anaesthetic drugs on free cytosolic calcium concentration in suspensions of isolated rat myocardial cells.