bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of body compartments on propofol induction dose in female patients
Authors: Chassard D. , Berrada K. , Bryssine B. , Guiraud M. , Bouletreau P.
Published: January 2009

Background: For induction of anaesthesia, drugs such as pro‐pofol are commonly administered according to a per weight basis. However, drugs are primarily distributed to the fat‐free mass. This study was undertaken to determine the relationship between propofol requirement for induction and body mass determined by bioimpedance analysis (BIA) or by body mass index (BMI).

Methods: Twenty‐one ASA 1 female patients scheduled for gynaecologic surgery received propofol for induction at 133 mg. min‐1. Stepwise regression analysis was used to describe the relationships between propofol requirement for loss of consciousness and age, body weight, and lean body mass measured by BIA and BMI (independent variables).

Results: Loss of consciousness was obtained with a propofol dose (Mean (SEM)) of 2.170.10 mgkg‐1. Stepwise analysis showed that propofol requirement (total dose) was not proportional to weight or age but related to lean body mass as determined by BIA and to body mass index (r2 = 0.447; global P‐ value <0.007). BMI was the only regressor variable when the propofol dose was expressed in mg. kg‐1 (r2 = 0.661; P<0.001).

Conclusions: Our results indicate that propofol requirements for induction are proportional to the lean body mass rather than total body weight.
Pulmonary vascular effects of nitroglycerin and isosorbide dinitrate in patients with end‐stage cardiomyopathies
Authors: Muikku O. , Hynynen M. , Salmenperä M. , Nieminen M. S.
Published: January 2009

Background: Severe preoperative pulmonary hypertension predicts a poor outcome after heart transplantation and therefore pulmonary vasoreactivity is frequently evaluated in the pretransplantation screening. Among the i.v. organic nitrates used in this evaluation, isosorbide dinitrate and nitroglycerin differ in their pharmacokinetics, and isosorbide dinitrate has been suggested to be more selective in its effects on pulmonary vasculature than nitroglycerin.

Methods: Haemodynamic effects of nitroglycerin and isosorbide dinitrate were compared in 8 patients with end‐stage cardiomyopathy. Each patient was given increasing i.v. infusion‐doses of the two nitrates in a random order and double‐blind and cross‐over fashion until the target of at least 25% decrease in mean pulmonary artery pressure was achieved.

Results: A total dose of 11 (3–20) (mean, 95% confidence interval) μg kg‐1 of nitroglycerin and that of 87 (12–161) μg kg‐1 of isosorbide dinitrate were given during the infusions of 20 (14–27) and 28 (18–37) min duration, respectively. With these doses producing similar acute decreases in mean pulmonary artery pressure, both nitroglycerin and isosorbide dinitrate also showed equal effects on pulmonary and systemic vascular resistances as well as on other systemic and right ventricular haemodynamic parameters.

Conclusion: We conclude that there is no difference between i.v. nitroglycerin and isosorbide dinitrate in their selectivity on the pulmonary vasculature in patients with end‐stage cardiomyopathy.
Transoesophageal echocardiographic evaluation of ventricular function during transvenous defibrillator implantation
Authors: Poelaert J. , Jordaens L. , Visser C. A. , Clerck C. De , Herregods L.
Published: January 2009

Background: Intraoperative testing and defibrillation threshold determination may jeopardise patients, scheduled for implantation of a cardioverter‐defibrillator (ICD). The purpose of this study was the assessment of the influence of consecutive defibrillation attempts on left ventricular systolic and diastolic function by means of transoesophageal echocardiography (TEE).

Methods: Eighteen patients with malignant ventricular arrhythmias that were resistant to antiarrhythmic drugs were monitored with TEE before, during and after implantation of a cardioverter‐defibrillator. Left ventricular fractional area contraction as a measure of ejection fraction was assessed before and after each defibrillation attempt. Transmitral and right upper pulmonary venous flow parameters were evaluated before and after the whole implantation procedure.

Results: Adequate data were available in 14 patients during 4 consecutive attempts. No major alterations were observed in heart rate or fractional area contraction, measured at 30 s and 3 min after defibrillation. Overall, the ratio of early‐to‐late transmitral filling decreased significantly after the implantation procedure (from 0.91±0.12 to 0.82±0.14; P<0.05). Systolic pulmonary venous flow velocity decreased from 0.49±0.11 to 0.41±0.10 m/s (P=0.04); this decrease was observed in both groups. A significant increase of the atrial contraction wave (from 0.25±0.06 to 0.34±0.07 m/s; P<0.03) was seen. Subdividing patients related to their preoperative ejection fraction, a significant decrease of the early‐to‐late transmitral filling of the LV was revealed in patients with ejection fraction less than 35% (group 1). Also, a significantly lower systolic fraction of the pulmonary venous flow after ICD implantation in conjunction with a significantly longer diastolic flow time was shown in this patient group in comparison with patients with a preoperative ejection fraction of more than 35% (group 2).

Conclusion: Defibrillation threshold testing of the ICD system changes LV inflow characteristics and impedes diastolic function of the left ventricle and may thus precipitate heart failure by this mechanism. No deleterious effects of threshold testing were observed with respect to fractional area contraction nor any deterioration of LV function was found in a clinically significant amount due to consecutive defibrillation attempts.
Metabolic, ventilatory and circulatory effects of doxapram in anaesthetized pigs during normoxia and hypoxia
Authors: BjÖrk L. , Arborelius M. , Renck H. , Rosberg B.
Published: January 2009

Background: In a previous clinical study doxapram was found to improve ventilatory efficacy postoperatively, presumably via effects on hypoxic pulmonary vasoconstriction (HPV). The present study was designed to see whether doxapram induced any changes of arterial oxygenation and pulmonary vascular resistance during normoxia or hypoxia and whether the changes were influenced by the anaesthetic agents.

Methods: Seventeen piglets were anaesthetized by combinations of either midazolam + fentanyl + pancuronium + pentobarbital (TIVA, n = 9), or by midazolam + fentanyl + pancuronium + halothane, 0.5% in end‐tidal gas (Hal, n = 8). Analyses of expired gas and mixed venous and arterial blood in combination with determinations of central blood flow and pressures allowed for calculations of standard metabolic, ventilatory and circulatory data. Values were obtained at normoventilation using normoxic (FIO2 = 0.3) and hypoxic (FIO2 = 0.08) gas mixtures at calculated doxapram plasma concentrations of 1, 2 and 4 μg · ml‐1.

Results: With few exceptions doxapram administration affected the investigated variables only moderately during normoxia. In group Hal, PVR and SVR showed a biphasic raise (P< 0.05), CO fell (P< 0.05‐P≥ 0.05) and C(a ‐v)O2 rose (P<0.05). In group TIVA, PaO2 fell (P<0.01‐0.05) despite unchanged PVR, CO and VD/VT. Hypoxia affected a moderate increase in PVR in group TIVA (P<0.05), which was slightly lower at the lowest and highest plasma levels of doxapram (P<0.05). In group Hal, the induction of hypoxia induced a more pronounced rise in PVR (P<0.05) which showed a biphasic response to increasing dose levels of doxapram, the lowest dose affecting a further rise (P<0.05) and the highest a reduction to values below hypoxia control levels (P<0.05). Pronounced differences between the two groups with respect to values for metabolic and circulatory variables make the interpretation of data difficult.

Conclusions: Doxapram administration to anaesthetized animals did not induce any effects indicative of augmentation of the HPV response.
Preoperative ketorolac administration has no preemptive analgesic effect for minor orthopaedic surgery
Authors: Vanlersberghe C. , Lauwers M. H. , Camu F.
Published: January 2009

The utility of preoperative ketorolac administration to reduce the intensity and duration of postoperative pain was compared with placebo in a randomized double‐blind design of 60 ASA 1–2 patients scheduled for minor orthopaedic surgery. No opioids nor local anaesthetic blocks were used during surgery. The patients received either 30 mg ketorolac IV before surgery followed by a placebo injection after surgery or the reverse. Postoperative pain intensity was assessed repeatedly for 6 h using a visual analogue scale. No differences in pain intensity were observed between the two groups except for the initial 15‐min postoperative assesments in the ketorolac group. The time to first rescue morphine administration and the total morphine consumption during the 6‐h observation period were similar. It is concluded that the preoperative administration of ketorolac did not provide a significant preemptive analgesic benefit with regard to postoperative pain relief and opioid dose‐sparing effect.
Postoperative seizure‐like activity following sevoflurane anesthesia
Authors: Terasako K. , Ishii S.
Published: January 2009

Generalized clonic and tonic seizure‐like movements were observed during emergence from anesthesia with sevoflurane in a 32‐year‐old man.

The movements lasted 40 sec and necessitated no therapy. There were no significant effects of the incident on the cardiovascular system, such as hypotension, arrhythmia or bradycardia.

No neurological abnormalities were obvious after the anesthesia.

The movements may have been the result of seizure activity in the central nervous system, or myoclonus of the whole body.
Effects of epidural analgesia on gastroduodenal motility Experimental and clinical studies with epidural morphine and epidural bupivacaine
Authors: Thorn S.‐E.
Published: January 2009

Abstract: These investigations were undertaken to study the effects of epidural analgesia with morphine and bupivacaine on gastrointestinal motility and to evaluate if the effect of morphine after epidural administration is a central or peripheral effect. Comparative studies were performed in volunteers, postoperative patients and pigs. Gastroduodenal motility was evaluated by manometry, electromyography (EMG) and external electro‐gastrography (EGG). Gastric emptying was studied by an absorption test (acetaminophen) and orocecal transit time by the hydrogen breath test after ingestion of raffinose. In one study, intrathecal and intramuscular morphine were given simultaneously in an effort to receive plasma concentration of morphine comparable to that after an epidural administration. This combination was compared with intrathecal morphine alone to evaluate if the gastrointestinal effects were mediated by central or peripheral mechanisms.

Epidural morphine delayed gastric emptying in healthy volunteers and in postoperative patients. Thoracic epidural bupivacaine with sensory block of the dermatomes T3‐T12 did not influence gastric emptying. Orocecal transit time was prolonged after epidural morphine compared to epidural bupivacaine. Duodenal contractile activity was significantly increased in volunteers after epidural morphine compared to epidural bupivacaine. The pressure activity seen after epidural morphine was not always propulsive and retrograde activity occurred frequently. Gastric activity measured by EMG and EGG was significantly disturbed after intrathecal and epidural morphine and tachygastria was frequently seen. Intramuscular administration of morphine during intrathecal morphine resulted in additive effects.

These studies have shown that epidural morphine compared to epidural bupivacaine delays gastric emptying and prolongs orocecal transit time. These effects may be explained by the disturbed gastroduodenal motility seen after epidural morphine. The gastroduodenal effects of epidural morphine may be caused by both a central and a systemic effect of morphine.
Analgesia following arthroscopy — a comparison of intra‐articular morphine, pethidine and fentanyl
Authors: SODERLUND A. , WESTMAN L. , ERSMARK H. , ERIKSSON E. , VALENTIN A. , EKBLOM A.
Published: January 2009

It has recently been reported that morphine given in low doses intra‐articularly can produce significant analgesia in patients undergoing arthroscopic knee joint surgery. Data are lacking on the effect of other opioids using a local approach for drug delivery.

We studied the analgesic effect of intra‐articular opioids in 70 patients, divided into 7 groups, subjected to arthroscopic knee surgery in general anesthesia. The dimension of the study was based on a power of 0.8 to detect a 25% difference in pain intensity between those receiving opioids locally versus systemically (a=0.05 and β = 0.20). Following surgery, but before terminating anesthesia, the patients received one of the following combinations: 1 mg morphine intra‐articularly (i.art.) + saline intramuscularly (i.m.), 10 mg pethidine i.art + saline i.m., or 10 ug fentanyl i.art + saline i.m. In three additional groups the three opioids were given i.m. and saline given i.art. An additional control group received saline i.art. + i.m.

We did not find any significant difference between the groups considering postoperative pain intensity, need for analgesics or considering time to standing/walking or to discharge, analysing each opioid independently. There was, however, a tendency for pethidine i.art. to produce the lowest pain scores both at rest and during movement (P= 0.06). If analysing the results with regards to if opioids were given intra‐articularly or systemically, not considering the type of opioid given, we did however, find a significantly lower total sum of pain scores at movement following local administration (P< 0.05). No specific side‐effects were detected. We conclude that pethidine given intra‐articularly merits further investigation with respect to postoperative analgesia following the activation of peripheral opioid mechanisms.
Long‐term intrathecal infusion of morphine in the home care of patients with advanced cancer
Authors: GESTIN Y. , VAINIO A. , PÉGURIER A. M.
Published: January 2009

Background: Fear of infections and other complications has made many clinicians avoid intrathecal application of morphine in chronic cancer pain. However, recent comparative studies show that, in long‐term treatment, intrathecal morphine administration may give a more satisfactory pain relief with lower doses of morphine and fewer side‐effects than epidural administration. In Montpellier Cancer Institute, first cancer pain patients received long‐term intrathecal morphine as early as in 1979, and since then more than 400 patients have been treated.

Methods: In 1991–1994, 50 patients having refractory cancer pain were treated with a continuous intrathecal infusion of morphine using an external pump with patient‐controlled boluses. In this retrospective study, the outcome of these 5602 days of morphine therapy will be analysed. The treatment consisted of a lateral puncture technique, strictly aseptic conditions during catheter insertion and changes of pump reservoirs, and effective prevention of side‐effects.

Results: The average duration of intrathecal infusion was 142 (7–584) days. The mean starting dose, 2.5 (0.4–8.3) mg/day, increased to a mean final dose of 9.2 (1–94) mg/day, the average dose being 5.4 (1–23) mg/day. During the treatment period, no clinically detectable infections and no respiratory depression occurred. Leakage of cerebrospinal fluid followed by post‐spinal headache occurred in only 6 patients who received a temporary external catheter: the lateral lumbar puncture technique seemed to protect from this complication in long‐term treatment. The patients stayed at home, coming to agreed control visits only at 4–6‐week intervals, using a telephone‐telefax service for emergencies.

Conclusions: Long‐term intrathecal morphine infusion seems to provide satisfactory analgesia, few side‐effects and a high degree of patient autonomy.
Epidural analgesia following upper abdominal surgery: United Kingdom practice
Authors: COOK T. M. , EATON J. M. , GOODWIN A. P. L.
Published: January 2009

Background: Epidural Analgesia (EA) may be used to provide pain relief after upper abdominal surgery. A variety of drugs and combinations may be used. Potential side effects lead some to believe EA should be restricted to high care areas.

Method: The use of EA following upper abdominal surgery is surveyed in 214 hospitals in the United Kingdom by means of a postal questionnaire.

Results: Sixty‐seven percent use EA frequently and 3% not at all. The low thoracic site is the most commonly used, by 65%. Forty‐eight percent use a combination of sites. EA is most frequently achieved using a mixture of an opioid and a local anaesthetic (97%). No other agents are used. Fentanyl and diamorphine are the opioids used most widely (61% and 52% departments, respectively) in combination with local anaesthetic. Subcutaneous heparin is regularly used in 89% of departments. In 43%, the epidural is sited shortly after administering heparin. Use of EA is restricted solely to intensive or high‐care units in 46% of hospitals. In 82% of departments, EA is continued for up to 72 h. Ninety‐six percent of departments use continuous epidural infusions in the postoperative period. Adjunct analgesia includes non‐steroidal anti‐inflammatory drugs in 50% of departments. An anaesthetist supervises EA in 89% of hospitals. EA is considered to be the best mode of analgesia available by 80% of respondents.

Conclusion: EA is widely used in the United Kingdom following upper abdominal surgery. A degree of consensus exists on the choice of drug types, their method of administration and duration. There is no consensus as to whether the technique should be used on a general ward, which opioid should be used or the timing of heparin.
Scintigraphic visualization of intrathecal liposome biodistribution
Authors: UMBRAIN V. , D'HAESE J. , ALAFANDY M. , DE ROOVER E. , SCHOUTENS A. , VAN GANSBEKE B. , ALBERT A. , GOFFINET G. , CAMU F. , LEGROS F. J.
Published: January 2009

Background: Liposomes containing local anaesthetics have been administered intrathecally and in the epidural space. Poor attention has been given to the pharmacokinetics of liposomes as drug carriers. Therefore, we observed the biodistribution of liposomes after intrathecal injection in rats by scintigraphic imaging during 24 h.

Methods: We administered 99Tc‐labeled multilamellar (MLV) and small unilamellar vesicles (SUV) of defined size and volume dispersities into the cerebrospinal fluid at the lumbar level. Those vesicles were free of contamination by radiolabeled colloids as visualized by light and electron microscopy and of neurotoxic products from phosphatidylcholine hydrolysis and peroxidation, both during the preparation process and after 24 h incubation in cerebrospinal fluid at 37°C in vitro.

Results: SUV immediately diffused from the lumbar site of injection to the head and were cleared between 1 and 24 h after injection. MLV were cleared more slowly from the spinal space and appeared in the head region 1 h after injection where they accumulated up to 24 h. These differences were explained in terms of vesicle sizes and volumes. SUV with 0.05 μm diameters were rapidly absorbed into the blood through the arachnoid granulations. In contrast, particles larger than the upper size limit of the arachnoid granulations permeability (±8 μm) could accumulate in the head with a slow elimination rate.

Conclusion: This difference in clearance from the intrathecal space outlines the importance of defining the size of the liposomes, the distribution of a tracer or a drug inside the liposomal preparation, the chemical stability and the absence of toxic degradation products of liposome formulations before clinical use.
Prevention of hypertension during trans‐sphenoidal surgery — the effect of bilateral maxillary nerve block with local anaesthetics
Authors: CHADHA R. , PADMANABHAN V. , ROUT A. , WAIKAR H. D. , MOHANDAS K.
Published: January 2009

Background: Severe cardiovascular responses are known to occur during trans‐sphenoidal excision of the pituitary gland despite adequate depth of anaesthesia. This study was undertaken to evaluate the effects of bilateral maxillary nerve block with local anaesthetics on the cardiovascular responses to various stimuli during this procedure.

Methods: In a group of 32 patients, 5–10 ml of a mixture of bupivacaine 0.5% and lignocaine 2% (1:1) was injected in the pterygopalatine fossa after induction of general anaesthesia. Seven control group patients did not receive any nerve block. In all the patients, general anaesthesia was induced with thiopentone and maintained with nitrous oxide‐oxygen, pentazocine, boluses of thiopentone and halothane. Pancuronium was used for neuromuscular blockade.

Results: In both the groups, maximum hypertension occurred on opening the blades of the bivalve nasal speculum. In the study group, hypertensive response was signify cantly less following nasal infiltration with adrenaline containing solution (10.26% increase vs. 23.08% in the control group, P < 0.05), nasal dissection (2.82% vs. 9.45%, P < 0.01) and on application of the nasal speculum (14.93% vs. 35.16%, P < 0.01). The effect on heart rate response was not significant.

Conclusion: The described technique is a useful adjunct to general anaesthesia for suppressing the haemodynamic responses during trans‐sphenoidal surgery.
Hemodynamic, sympathetic and angiotensin II responses to PEEP ventilation before and during administration of isoflurane
Authors: ANEMAN A. , PONTEN J. , FANDRIKS L. , EISENHOFER G. , FRIBERG P. , BIBER B.
Published: January 2009

Background: Positive end‐expiratory pressure (PEEP) ventilation and isoflurane anesthesia may opposingly affect the sympathetic nervous and renin‐angiotensin systems. This study was performed to elucidate the modulatory effects of isoflurane anesthesia on the neurohumoral and cardiovascular responses to PEEP.

Methods: Renin‐angiotensin and sympathetic nervous activity were investigated in mechanically ventilated, normovolemic, chloralose anesthetized pigs before and during administration of 1.4% isoflurane. Arterial angiotensin II (All) concentrations were measured and systemic, mesenteric, hepatic and renal spillover of norepinephrine (NE‐SO) were calculated using isotope dilution. Regional hemodynamic variables were investigated in parallel.

Results: PEEP10 alone moderately elevated All levels (+12.5 ± 4.9 pg/ml, P < 0.05) and increased systemic (+22±2.9 pmolmin100g‐1, P < 0.05) and notably mesenteric (+32±9.6 pmolmin100g‐1, P < 0.05) NE‐SO. Blood flow decreased in all vascular beds studied. Except for in the liver, isoflurane generally reduced NE‐SO compared to baseline but did not change All concentrations. Strikingly, the sympathoexcitatory response to PEEP10 was inhibited, whereas All increased markedly (+284±64 pg/ml, P < 0.05) during PEEP10 and isoflurane. Renal blood flow was significantly more reduced during PEEP10 and isoflurane compared to PEEP10 alone, whereas the magnitude of reductions were similar in the other vascular beds.

Conclusion: The data suggest that renin‐angiotensin activation is important to attenuate the impact of PEEP ventilation on cardioavascular performance during administration of the sympathodepressant isoflurane. Interference with the renin‐angiotensin system may cause cardiovascular decompensation in isoflurane anesthetized patients subjected to PEEP‐ventilation.
Effects of volatile anesthetics on the calcium ionophore A23187‐mediated alterations in hepatic flow and metabolism in the perfused liver in fasted rats
Authors: ARAKI M. , INABA H. , KON S. , IMAI M. , MIZUGUCHI T.
Published: January 2009

Alterations in intracellular calcium homeostasis have been implicated in hepatic injury. Volatile anesthetics modulate the homeostasis of intracellular calcium.

The effects of volatile anesthetics on the hemodynamic and metabolic alterations induced by the calcium ionophore A23187 were studied using isolated liver perfusion in fasted rats. The liver was isolated from 24 hr‐fasted male Sprague‐Dawley rats, and perfused through the portal vein at a constant pressure of 1.2 kPa in a recirculating perfusion‐aeration system. Halothane, isoflurane and sevoflurane were administered at 2%, 3% and 4.4%, respectively.

All volatile anesthetics maintained basal hepatic flow, reduced oxygen consumption, and transiently enhanced net lactate production. A23187 at initial concentrations of 0.8 to 3.2 μM decreased hepatic flow and oxygen consumption in a dose‐de pendent manner, and enhanced lactate production. All anesthetics significantly attenuated the decreases in hepatic flow and oxygen consumption after administration of A23187 at 1.6 μM. None of the anesthetics significantly influenced the A23187‐induced enhancement of net lactate production.

Volatile anesthetics may attenuate the hepatic vasoconstriction and oxygen debt induced by intracellular calcium overload.
A comparison of pressure‐ and volume‐controlled ventilation at different inspiratory to expiratory ratios*
Authors: LUDWIGS U. , KLINGSTEDT C. , BAEHRENDTZ S. , HEDENSTIERNA G.
Published: January 2009

Background: Inverse ratio ventilation (IRV) is frequently used in severe acute respiratory failure. IRV may lead to intrinsic positive end‐expiratory pressure (PEEP) and is thought to improve oxygenation and to have advantageous effects on lung mechanics. Published data to support the use of IRV are scarce. This animal study compares external PEEP with intrinsic PEEP in pressure‐ and volume‐controlled ventilation.

Methods: Fifteen pigs were randomly treated with 1. volume‐controlled PEEP ventilation (I:E ratio 1:2) (VCV PEEP), 2. volume‐controlled ventilation (I:E ratio 4:1) (VCIRV) and 3. pressure‐controlled ventilation (I:E ratio 4:1) (PCIRV). Baseline measurements were performed using volume‐controlled ventilation (I:E ratio 1:2) (VCV ZEEP). Lung mechanics, haemo‐dynamics and gas exchange were measured by standard methods and functional residual capacity (FRC) by the sulphur hexafluoride technique.

Results: In comparison to VCV PEEP, PCIRV resulted in reduced peak airway pressure (32±3 vs. 27±6 cm H2O, P < 0.001) and increased mean airway pressure (14±2 vs. 22±5 cm H2O, P < 0.001). FRC was 942±264 ml in VCV PEEP and 1024±390 ml in PCIRV (n.s.). Oxygen delivery was lower in PCIRV (458±193 vs. 346±150 ml/min, P < 0.05). Physiologic dead space was 14±4% in PCIRV and 20±6% in VCV PEEP and VCIRV (P < 0.005).

Conclusions: Inverse ratio ventilation did not result in improved FRC in comparison to conventional volume‐controlled PEEP ventilation. PCIRV allows for a reduction in minute ventilation but the increase in mean airway pressure compromises circulation.
Intravenous vitamin K1 prior to orthotopic heart transplantation: effects in vivo and in vitro
Authors: BARNETTE R. E. , WENDLING W. W. , SCHWEIGER J. W. , BRISTER N. W. , SCHARTEL S. A. , CHEN D. , SHUMAN C. A. , MCCLURKEN J. B. , JEEVANANDAM V.
Published: January 2009

Background: Vitamin Kj is used to reverse warfarin's anticoagulant action. It is unclear whether intravenous vitamin K1 is safe or efficacious prior to urgent cardiac surgery.

Methods: We retrospectively and prospectively examined the effects of preoperative intravenous vitamin K1 in vivo (administered for warfarin reversal immediately before heart transplantation) on intraoperative blood product utilization, hemodynamics and coagulation parameters. We also determined the direct effects of vitamin K, in vitro on rings of human saphenous vein and internal mammary artery.

Results: In the retrospective limb, 29 of 67 patients were administered vitamin K1 preoperatively via slow intravenous infusion. Vitamin K1 administration produced no adverse outcome but did not affect subsequent perioperative use of blood products. In the prospective limb (n=10), vitamin Kx significantly (P≤0.01, Student t‐test) altered mean arterial pressure (from 85±15 to 76±16 mmHg), systemic vascular resistance (from 1364±308 to 1078±252 dyn s cm‐5), and cardiac index (from 2.3±0.3 to 2.7±0.3 L/min/m2) (mean±SD). Significant decreases in prothrombin time (19.8±2.7 to 17.7±1.8 s) and ac tivated clotting time (164±26 to 137±24 s) were observed at 60 min. In vitro, vitamin K1 (10‐7 to 10‐4 M) had no effect on the tone of noradrenaline‐constricted rings.

Conclusions: Vitamin K1 administered by intravenous infusion prior to heart transplantation, did not alter subsequent perioperative blood product administration. Vitamin K1 rapidly reversed the anticoagulant effect of warfarin and produced modest hemodynamic changes. The decrease in systemic vascular resistance is probably not due to a direct effect of vitamin K1 on vascular smooth muscle.
Anesthesia of a patient with an obstructing tracheal mass: a new way to manage the airway
Authors: LICKER M. , SCHWEIZER A. , NICOLET G. , HOHN L. , SPILIOPOULOS A.
Published: January 2009

A case of upper airway obstruction due to thyroid tumor requiring surgery is presented. Successful establishment of an open tracheal airway was achieved by the insertion of an endotracheal stent and was followed 10 days later by tracheal resection and anastomosis.
NMDA receptor antagonists: interactions with opioids
Authors: DICKENSON A. H.
Published: January 2009

The N‐methyl‐D‐aspartate (NMDA) receptor for glutamate has been implicated in the generation and maintenance of central (spinal) states of hypersensitivity. Thus antagonists at this receptor‐channel complex have the potential not to totally abolish pain, but to prevent or block hyperalgesic states induced by tissue damage, inflammation, nerve damage and ischaemia. Information on amplification systems in the spinal cord such as the NMDA receptor is a step towards understanding why and how a painful stimulus is not always related to the response. There are now sufficient controlled clinical studies with agents such as ketamine to believe that, in humans, NMDA mediated events are critical in pathological and/or prolonged pain states. Consequently, use of antagonists may aid the treatment of difficult clinical pains when given alone or in combination with opioids. The combinations of opioids and NMDA antagonists may be especially helpful since some NMDA mediated events can be difficult to control with opioids alone (eg. neuropathic pain states). In addition, the ability of opioids to act presynap‐tically on C‐fibre terminals to reduce transmitter release produces synergistic inhibitions with postsynaptically acting NMDA receptor antagonists. Consequently, low dose combinations may be possible with low side‐effect liability. Finally, NMDA receptor activation would appear to be responsible for the generation of nitric oxide and prostanoids which further enhance pain transmission whereas adenosine release acts to control these NMDA mediated events. Thus, further targets for the indirect control of NMDA induced activity are possible.
β‐endorphin in the brain. A role in nociception
Authors: BACH F. W.
Published: January 2009

We have known the endogenous opioid peptide β‐endorphin for 20 years. Surprisingly, our knowledge of the physiological role of this peptide and its receptors in modulation of pain perception is still fragmentary. Whereas most studies have tried to elucidate the physiological role of β‐endorphin by reversing evoked responses by the opioid antagonist naloxone, this review focuses on quantification of release of β‐endorphin in the brain as the approach to define physiological and pathophysiological roles of β‐endorphin in relation to nociception. Using a lateral ventricle‐cisterna magna perfusion model in the anesthetized rat, it was shown that depolarization of neurons in the arcuate nucleus of the hypothalamus, where β‐endorphin is produced, was followed by release of β‐endorphin to the cerebrospinal fluid compartment. Intense activation of spinal nociceptive pathways by intrathecal capsaicin injections also led to β‐endorphin release. It is concluded that there may still be good reason to quantify β‐endorphin in human cerebrospinal fluid to elucidate the role of β‐endorphin in pain perception.
Cancer pain management
Authors: BRUERA E. , LAWLOR P.
Published: January 2009

Pain occurs in more than 80% of cancer patients before death. Because of the increase in the frequency of cancer deaths worldwide, it is imperative to address cancer pain as a public health problem. Until recently, educational efforts were focused on treatment issues rather than adequate assessment. The approach to pain intensity as a multidimensional construct has helped in focusing treatments and identifying prognostic factors. Valid tools have been developed that allow multidisciplinary assessment of these prognostic factors and their complex interrelationship with the analgesic response. As a result of increased opioid exposure, patients are currently developing newer toxicities, mostly central excitability including delirium, myoclonus, grand mal seizures, and hyperalgesia. The observation that more than 80% of patients will require alternate routes for opioid delivery before death led to the development of a number of novel and effective alternate routes for delivery. Finally, in recent years it has become evident that some specific pain syndromes need to be addressed using specific assessment and management techniques. Incidental pain, somatization, neuropathic pain, and cancer pain in patients with alcoholism and drug addiction are some of these syndromes.
Opioid responsiveness
Authors: HANKS G. W. , FORBES K.
Published: January 2009

Cancer pain generally responds in a predictable way to analgesic drugs and drug therapy is the mainstay of treatment. A small proportion of patients, of the order of 20%, have pain that does not respond well to conventional analgesic management. Because opioid analgesics are the most important part of this pharmacological approach, a terminology has developed which centres around whether or not pain will respond to opioid analgesics. The terms opioid‐responsive‐pain and opioid‐non‐responsive pain, or opioid‐resistant‐pain, have been used to differentiate between patients whose pain falls into these two broad groups. This terminology is not satisfactory because it implies an all or none phenomenon, that is that pain either does or does not respond to opioid analgesics. Rarely is there such a clear distinction in practice. This is because the end point when titrating dose against pain with strong opioid analgesics is not simply pain relief or lack of relief: adverse effects may limit dose titration.

It is preferable to describe patients with pain which is relatively less sensitive to opioids and/or patients where there is an inbalance between analgesia and unwanted effects as having “opioid‐poorly‐responsive pain”. A pragmatic definition of opioid‐poorly‐responsive pain is pain that is inadequately relieved by opioid analgesics given in a dose that causes intolerable side effects despite routine measures to control them. Included in this definition is so called paradoxical pain which is not a distinct entity.

Neuropathic pain is the most common form of opioid‐poorly‐responsive pain. The underlying pathophysiology remains unclear but abnormal metabolism of morphine is not the cause of a poor response to this drug.

Patients with opioid‐poorly‐responsive‐pain should be considered for treatment with the same opioid by an alternative (spinal) route or with an alternative opioid agonist administered by the same route (whether oral or parenteral), in conjunction with adjuvant analgesics such as tricyclic antidepressants. The most commonly used alternative oral opioids are phenazocine and methadone; transdermal fentanyl is an additional option.
International opioid consumption
Authors: CLAUSEN T. G.
Published: January 2009

The aim of the present study was to analyse the opioid consumption in the 10 most opioid‐consuming countries in relation to the Danish consumption.

The results revealed, that the total opioid consumption has increased in all of the 10 most opioid consuming countries (range 26–1423%). In Denmark, the total opioid consumption increased 353% from 1981 to 1993, exceeding 1.45 million defined daily doses per 1 million inhabitants in 1993, which is the highest in the world. Of these, morphine accounted for 39%, methadone 22%, ketobemidone 21% and buprenorphine 14%. The consumption of long‐acting opioids (morphine sustained release, methadone, buprenorphine) and short acting opioids (others) in creased 1427% and 105%, respectively. Analysis of a sample of 1854 prescriptions made by general practitioners for opioids revealed, that less than 10% of the prescriptions were issued for cancer pain conditions.

In conclusion of other countries consider Denmark as worthy of imitation concerning opioid treatment in cancer pain, attention should be paid to the pattern of the Danish opioid consumption, which is outstanding with respect to quantity.
Pharmacokinetics and pharmacodynamics of controlled‐release opioids
Authors: KAIKO R. F.
Published: January 2009

While pharmacokinetic/pharmacodynamic relationships for opioids have not been consistently demonstrable or sufficiently predictive, there remain compelling reasons to pursue such relationships. Among the reasons for pursuing pharmacokinetic/ pharmacodynamic relationships is the prospect of predicting the time‐action characteristics of new therapeutics on the basis of early studies in normals using pharmacodynamic surrogates for analgesia. The realization of such a model could improve the efficiency of development of analgesics.

Four studies involving 98 normals were conducted to determine whether significant and reproducible relationships existed for oxycodone in the form of an oral controlled‐release tablet. All studies were analytically blinded and utilized a validated gas chromatographic/mass spectrometric, sensitive (0.2 ng/ml), and specific method for oxycodone (four studies) and oxymorphone (two studies) quantitation in 17 to 20 serial plasma samples over 36 to 48 hours following a single 20 mg (or 40 mg) dose in each study. Concurrent assessments included vital signs and opioid effect VAS questionnaires. The studies demonstrated significant relationships between plasma oxycodone (but not oxymorphone) and pharmacodynamic surrogates (particularly VAS “drug effect”) and were predictive of the 12‐hour duration of pain control and prompt onset of analgesia subsequently demonstrated in multiple clinical studies involving patients with various pathological pain syndromes.

The results suggest that investigators can make earlier, accurate predictions of opioid analgesic pharmacodynamics in patients based on pharmacokinetic/ pharmacodynamic studies in normal volunteers.
Opioid use in chronic pain
Authors: MCQUAY H. J.
Published: January 2009

Many of the important questions for those who prescribe opioids in chronic pain, and important for those who take the drugs, still have to be answered with inadequate evidence, because we lack randomised trials on these topics. Two of the principal reasons for ‘failure’ of opioids to relieve pain, incident pain and neuropathic pain, are discussed. Some specific adverse effect problems are addressed, and the paper concludes with a section on the vexed issue of opioid prescription in non‐cancer pain.
Tolerance and dependence to opiates
Authors: JASINSKI D. R.
Published: January 2009

In the 19th century, investigators recognized that addiction to opiates involves tolerance and dependence. In the United States, the National Academy of Sciences and the Public Health Service initiated systematic investigations into opiate addiction in 1929. Tolerance and dependence to morphine, the prototype for opiate drugs, were the emphasis of human studies for the next fifty years. This presentation highlights salient features of tolerance and dependence learned in these studies and relates these findings to clinical use in treating pain.
Pharmacological approaches other than opioids in chronic non‐cancer pain management
Authors: MERSKEY H.
Published: January 2009

Many pains are controlled by non‐addictive procedures ranging from exercise to a variety of analgesic medications. Some pains are controlled by analgesic drugs, but at the cost of intolerable side effects. This is true both for non‐steroidal anti‐inflammatory drugs and opioids. The worst pains are most often controlled by opioids, but problems of tolerance and addiction limit these successes. This contribution provides a statement on non‐addictive, non‐opioid drugs which help to control pain. Just as these vary in their success, so they vary also in the strength of the scientific evidence which supports their use. The groups of drugs to be considered can be evaluated in three respects; evidence of analgesic effect in controlled trials; evidence of side‐effects compared with control substances and with standard experience; evidence of usefulness in clinical practice. The latter which is the most important for practice often has the least scientific proof.

Six main classes of drugs are recognized which provide analgesic effects, other than opioids. 1) Non‐steroidal anti‐inflammatory drugs are widely accepted as analgesics on the basis of animal studies, numerous controlled investigations and clinical practice. Acetaminophene may not be anti‐inflammatory, but is recognized as an effective analgesic which in many other respects resembles the above. 2) Muscle relaxants, e.g. cyclobenza‐prine or baclofen have varied actions, but often provide some relief of pain. 3) Antidepressants may be analgesic if they relieve depression which is giving rise to pain. This applies to all antidepressants. Some antidepressants have been shown to be analgesic in the absence of depression. The best accredited of these is amitriptyline. Antidepressants too have significant side effects. A serotoninergic hypothesis is insufficient to explain the actions of antidepressants in relieving pain in the absence of depression. 4) Phenothiazine neuroleptics (and possibly some others) may be analgesic. Drugs reported to be analgesic include chlorpromazine, fluphenazine, perphenazine, trifluoperazine, methotrimeprazine (levomepromazine) among others. Halope‐ridol has also been utilized. Well controlled evidence exists with the use of methotrimeprazine (levomepromazine) used as an injection. The analgesic effect of oral neuroleptics is less well established and mostly depends upon clinical observation, withdrawal and re‐challenge. 5) Anticonvulsants. 6) Other drugs. Non‐steroidal anti‐inflammatory drugs and some muscle relaxants, e.g. cyclobenzaprine are best used in the short term. The gastrointestinal side effects of non‐steroidal anti‐inflammatory drugs have been quite troublesome and over 2% of patients followed over five years are at risk of developing peptic ulceration from such medication. Cyclobenzaprine is best used in short term treatment, but may be used intermittently for chronic pain. Antidepressants, neuroleptics, anticonvulsants and some other drugs can be used long term. Topical analgesic agents may also be used.
A retrospective analysis of nitric oxide inhalation in patients with severe acute lung injury in Sweden and Norway 1991–1994
Authors: LUHR O. , NATHORST–WESTFELT U. , LUNDIN S. , WICKERTS C.–J. , STIERNSTRÖM H. , BERGGREN L. , AARDAL S. , JOHANSSON L.–Å. , STENQVIST O. , RUDBERG U. , LINDH A. , BINDSLEV L. , MARTLING C.–R. , HORNBAEK V. , FROSTELL C.
Published: January 2009

Background: Patients with severe acute lung injury (ALI) have been treated compassionately on doctors' initiative with inhaled nitric oxide (INO) in Sweden and Norway since 1991. In 1994 the previously used technical grade nitric oxide was replaced by medical grade nitric oxide.

Methods: We have carried out a retrospective data collection all identified adult patients treated with IN0 for >4 h during the period 1991‐1994 focusing on safety aspects and patient outcome. We used the following exclusion criteria (1) Age <18 years, Simultaneous treatment with extracorporeal removal of CO2 NO inhalation period <4 h, (4) Incomplete or missing patient charts, (5) Use of IN0 in order to treat pulmonary hypertension following cardiac surgery, with little or no acute lung injury.

Results: Inclusion criteria were met by 56 out of 73 identified patients. Mean age was 48219 years and the median duration of IN0 treatment was 102 h. PaOz/FIOz ratio at start of treatment was 85233 mm Hg with a lung injury score (LIS) of 3.2t0.8. The aetiology of the lung injury was pneumonia (n=27), sepsis (n=12) and trauma (n=8). Survival to hospital discharge was 41% and survival after 180 d was 38%. Three serious adverse events were identified, two from technical failures of the IN0 delivery device and one withdrawal reaction necessitating slow weaning from INO. No methaemoglobin values >5% were reported during treatment.

Conclusion: The overall mortality did not differ dramatically from historical controls with high mortality. Only a randomised study may determine whether IN0 as an adjunct to treatment alters the outcome in severe ALL One cannot at present advocate the routine use of IN0 in patients with ALI outside such studies.
Perioperative myocardial ischemia is associated with a prolonged cardiac vagal dysfunction after non–cardiac surgery
Authors: DWORSCHAK M. , GASTEIGER P. , VAN ACKERN K.
Published: January 2009

Background: Heart rate variability (HRV), a measure of cardiac autonomic balance seems to be linked to coronary artery disease (CAD). Impaired vagal input facilitates the generation of fatal arrhythmias and has a great impact on morbidity and mortality. The purpose of this study was to determine the relationship between perioperative HRV and the incidence of silent myocardial ischemia (SMI) and ventricular dysrhythmias in CAD–patients undergoing non–cardiac surgery.

Methods: 31 patients were studied by continuous Holter electrocardiography preoperatively and again on the evening before surgery until postoperative day 3. Three frequency and one time domain measures of HRV (TP, 0.01–1.00 Hz: total power of the amplitude spectral plot; LF, 0.04–0.15 Hz: low–frequency power; HF, 0.15–0.40 Hz: high–frequency power; MeanRR: mean of all coupling RR–intervals between normal beats) as well as ischemic events and ventricular couplets and runs were computed.

Results: Depending on the presence of ischemic episodes, each patient was assigned to either the no SMI–group (13 pts) or the SMI–group (18 pts). MeanRR, TP and LF significantly declined in both groups over time. The parasympathetically dominated index HF, however, only decreased in the SMI–group. Normalized HF power (HF/TP) even increased in the no SMI–group resulting in a postoperative decrease in LF/HF ratio. TP, LF, and HF inversely correlated with ischemia parameters whereas HF/ TP and HF/LF ratio correlated with the number of ventricular couplets. Incidence and severity of SMI significantly increased after surgery.

Conclusion: Postoperatively, a prolonged vagal withdrawal occurred in CAD–patients exhibiting perioperative SMI. Whether the increased incidence of SMI after surgery in conjunction with the observed parasympathetic derangement contributes to adverse cardiac outcome still has to be determined.