bluuebunny/crossref_metadata_2025 huggingface dataset:
High‐frequency oscillatory ventilation combined with intermittent mandatory ventilation in critically ill neonates and infants
Authors: Murthy B. V. S. , Petros A. J.
Published: January 2009

We have evaluated the high‐frequency oscillatory ventilation (HFOV) combined with intermittent mandatory ventilation (IMV) in critically ill neonates and infants using the Babylog 8000 SW 4.0.

We used HFOV combined with IMV as a rescue mode in 10 neonates and infants aged 1 day to 17 months, who were receiving maximal conventional ventilation for severe respiratory failure.

There was a significant reduction in inspired oxygen requirement when starting HFOV combined with intermittent mandatory ventilation (IMV), from a baseline mean of 0.90 (CI95 0.79‐1.01) to 0.55 (CI95 0.40‐0.71) at 6h and 0.44 (CI95 0.37‐0.52) at 12h. There was also an overall improvement in gas exchange with complete haemodynamic stability.

These data suggest that HFOV‐IMV mode offers significant improvement as a rescue mode for neonates and infants with severe respiratory failure.
Deformed spinal needle tips and associated dural perforations examined by scanning electron microscopy
Authors: Jokinen M. J. , Pitkänen M. T. , Lehtonen E. , Rosenberg P. H.
Published: January 2009

Background: The tips of modern thin Quincke‐type spinal needles may be easily damaged by bone contact during the puncture. The purpose of this study was to find out the frequency of tip deformation in routine clinical work and the appearance of the dural perforations made by such damaged needles.

Methods: Two hundred and ninety‐five Quincke‐type needles (22G‐29G) used in routine spinal anaesthesia were inspected by light microscopy. Scanning electron micrographs were taken of some of the damaged tips and of experimental dural perforations made by these.

Results: Four per cent of the needle tips were clearly bent or hooked and 11% were slightly bent. When an introducer needle was used (19 cases), one needle was clearly bent and one slightly bent. A puncture with a bone contact was associated with clear tip damage in 7%; a puncture without bone contact resulted in an undamaged or slightly bent needle tip in 99% of the cases. The numbers of bent tips among the various sizes were: 22G‐2/21, 25G‐13/40, 27G‐28/231, 29G‐1/3. In scanning electron microscopy (SEM) images of four clearly bent needle tips the deviation of the tip was between 10 μm and 20 μm. In SEM of eleven dural perforations, the holes made by needles with clearly bent tips were almost closed and three of them exhibited an “open tin can” appearance. None of the dural perforations was badly torn.

Conclusions: We verified that the tips of modern thin spinal needles are vulnerable to damage due to contact with bone. However, the holes made in dura by needles with bent tips do not appear to be excessively torn.
Continuous thoracic epidural analgesia versus combined spinal/thoracic epidural analgesia on pain, pulmonary function and the metabolic response following colonic resection
Authors: Scott N. B. , James K. , Murphy M. , Kehlet H.
Published: January 2009

Background: The neuroendocrine response following major surgery has not been previously influenced by either regional anaesthetic techniques or opioid analgesia probably due to insufficient intraoperative afferent neural blockade. In this study we attempted to determine whether significant inhibition of these pathways could be achieved by combining preoperative high spinal anaesthesia with postoperative thoracic epidural anaesthesia. In theory too, there may be additional benefits over perioperative thoracic epidural anaesthesia on pain and pulmonary dysfunction.

Methods: 20 ASA 1–3 patients undergoing elective colonic surgery were studied. Gp 1 (n=10) received a high spinal intraoperative block to T4 using 6mls of 0.5% bupivacaine plus continuous epidural 0.125% bupivacaine/0.0025% diamorphine. Gp 2 (n=10) patients received epidural 0.5% bupivacaine block to T4 plus continuous epidural infusion of 0.125% bupivacaine/0.0025% diamorphine. We measured a) plasma glucose and Cortisol at 0, 1, 2, 3, 4, 8 and 24 h; b) forced vital capacity (FVC), forced expiratory volume in the first second (FEV1) and peak flow rate (PFR) preoperatively, at 8 and 24 h; c) visual analogue pain scores (VAS 0–10) at rest, cough and mobilisation at 8 and 24 h; d) block height every hour for 12 hours then 3 hourly; e) 24‐hour urine volumes for dopamine, adrenaline and noradrenaline f) 24‐hour PCA morphine requirements.

Results: The two groups did not differ in age, sex, height, weight, duration of surgery, blood loss or serum albumin. Pain relief was excellent and similar in both groups. The average 24 hour morphine consumption was 10 mg in both groups with no differences in the block height. All the patients had a 30–50% reduction in FEV1, FVC and PFR (P>0.05). Metabolically, there was no statistical difference between the 2 groups except a higher rise in glucose in Gpl at 2 and 3 h (P=0.0312 and 0.014). 24‐hour catecholamine studies showed no differences for noradrenaline (P=0.8), adrenaline (P=0.47) and dopamine (P=0.36).

Conclusions: Thoracic epidural bupivacaine/diamorphine infusion provided excellent postoperative analgesia following colonic surgery. An intraoperative combined spinal/epidural technique conferred no additional benefit on analgesia, pulmonary function and the neuroendocrine response.
Dural puncture: the patients' perspective A patient survey of cases at a DGH maternity unit 1983–1993
Authors: Costigan S. N. , Sprigge J. S.
Published: January 2009

Background: This study was designed to investigate the patient experience following accidental dural puncture complicating obstetric epidural analgesia.

Methods: Sixty‐three patients who had suffered from accidental dural puncture during obstetric epidural analgesia over a ten‐year period were sent a questionnaire enquiring about their experiences. 68% responded.

Results: Headache was the most severe symptom, occurring in 86% of this group; it lasted for a median of eight days and recurred after discharge in 47%. Backache occurred in 70% and 58% suffered with backache following discharge.

Headache was considered to be the worst aspect by 49% of responders, backache by 19% and bedrest by 33%. Bed rest was frequently voluntary (as opposed to being enforced on medical orders) since many patients only gained relief from their headache when supine.

Twenty patients (47%) received a blood patch, which was effective in relieving headache in 14 patients; however, the headache recurred after discharge in 10 of these 14 patients. Only 8 patients (19%) stated that they were aware of the risk of dural puncture prior to their epidural, three of whom were members of paramedical professions.

Conclusions: Headache and backache are both common following dural puncture with a 16G needle and both frequently recur after discharge from hospital. It was the strongly expressed opinion of this selected group that all mothers should be warned of the risk of dural puncture before undergoing epidural analgesia.
Local anaesthesia and propofol‐fentanyl sedation for carotid artery surgery
Authors: Nordström O. , Potemkowski A. , Johansson R. , Ridder B. de , Sternlo J. E. , Larsson L. , Sandin R.
Published: January 2009

Background: In patients undergoing carotid artery surgery with local anaesthesia (LA), a sedative / analgesic pharmacological supplement is appropriate in most cases in order to provide comfort. This adjunct should not preclude continuous clinical neurological monitoring. The aim was to investigate if a combination of fentanyl and propofol to supplement LA would provide comfort for the patient, allow continuous clinical neurological monitoring and absence of difficulties for the anaesthetist, and good conditions for surgery, including insertion of a shunt if this should become necessary.

Methods: During a 1‐year period low doses of propofol and fentanyl were used to supplement LA in 36 cases of carotid artery surgery in 34 consecutive patients. A shunt was only used if neurological dysfunction occurred. Data on haemodynamics, pulmonary gas exchange, clinical neurological monitoring, and subjective opinions from patients, surgeons and anaesthetists were obtained. Morbidity within 30 days was documented.

Results: Conversion to general anaesthesia was undertaken in one patient, previously operated on the same artery, who became unconscious due to a stroke during manipulation of the artery before arteriotomy. No other adverse outcome was found within 30 days. In the remaining 35 cases the procedures were carried out under LA. Stump pressures below 50 mmHg were found in 17/35 cases. Intraoperative neurological dysfunction was detected in 10/35 cases (stump pressures between 23 and 60 mmHg). Shunting was easily performed, and rapidly relieved the neurologic symptoms in all these patients. Intraoperative respiratory and haemodynamic control was satisfactory. Ease of performance, including clinical neurological monitoring, was acknowledged by both anaesthetists and surgeons, and all 33 patients (35 operations) who were accessible for a postoperative interview stated that they would prefer the same regimen in the case of further surgery.

Conclusion: The number of cases in this open, uncontrolled study does not permit an evaluation of this anaesthetic and sedative technique in terms of neurological and cardiac outcome. Thus, we simply want to inform about our positive experiences regarding patient acceptance and ease of performance in all relevant respects when fentanyl and propofol are used to supplement LA for carotid artery surgery.
Propofol reduces emesis after sufentanil supplemented anaesthesia in paediatric squint surgery
Authors: Standl T. , Wilhelm S. , Knobelsdorff G. von , Esch J. Schulte am
Published: January 2009

Background. Squint surgery is associated with a high incidence of postoperative emesis. The purpose of this prospective study was to examine the influence of propofol and isoflurane anaesthesia on the incidence of postoperative nausea and vomiting in children.

Methods. Ninety children aged 3–10 years were randomly allocated to one of 3 groups. In all groups, children received 2 mg/kg propofol, 0.5 μg/kg sufentanil and 0.5 mg/ kg atracurium for induction of anaesthesia. In group 1, anaesthesia was maintained with 15–20 mg/kg·h propofol and children were ventilated with 30% O2 in air. In group 2, anaesthesia was maintained with 10–15 mg/kg·h propofol and 30% O2 in N2O. In group 3, anaesthesia was maintained with 1.0–1.5 Vol% isoflurane and 30% O2 in N2O. The time of extubation, awakening and postoperative surveillance, the incidence and numbers of episodes of postoperative nausea and vomiting were registered as well as requirements of antiemetics. Statistics were made using ANO‐VA and Chi‐square test or Kruskal‐Wallis test with P<0.05 considered as significant.

Results. The overall incidence of nausea (P=0.0001) and vomiting (P=0.002) was higher in group 3 (70%;73%) than in group 1 (13%; 23%) and 2 (20%;28%). Episodes of nausea (P=0.0001) and vomiting (P=0.0013) were more frequent in group 3 (74%;69%) than in group 1 (13%;15%) and 2 (13%;16%). Antiemetic requirements were higher and the time of postoperative sleep and surveillance was longer in group 3 than in group 1 and 2 (P=0.04).

Conclusion. Propofol‐sufentanil anaesthesia results in less emesis and treatment during the early postoperative phase irrespective of N2O administration compared with propofol‐ induced isoflurane anaesthesia and may be recommended in children undergoing squint surgery.
Age‐dependent development of acute tolerance to propofol and its distribution in a pharmacokinetic compartment‐independent rat model
Authors: Larsson J. E. , Wahlström G.
Published: January 2009

Background:Previous animal and clinical studies have shown a dose‐dependent increase in propofol concentrations in blood at wakening after propofol infusion. A development of an acute tolerance to propofol has been proposed. To elucidate this, brain concentrations of propofol at the time of an EEG end point was used as a measure of CNS sensitivity.

Methods:Twenty young or 20 old rats were assigned to either induction of anaesthesia with propofol or induction followed by maintenance of anaesthesia with intermittent propofol infusions during 60 minutes. All rats were killed at the EEG end point and samples of cerebral cortex, hippocampus, striatum, brain stem, cerebellum, blood, muscle and fat tissue were submitted to HPLC analysis of propofol concentrations. A new model describing the infusion requirements is introduced.

Results:The estimated infusion rate during maintenance declined exponentially with time at a slower rate in young compared with old rats. Old rats had higher propofol concentrations in blood, hippocampus, striatum, brain stem, cerebellum, muscle and fat after 60 minutes compared with induction. In contrast, young animals had no significant change in brain concentrations, but the propofol concentrations in muscle and fat were increased.

Conclusion:It is concluded that maintenance of propofol anaesthesia may alter the CNS sensitivity to propofol in old animals, i.e. an acute tolerance may develop. Young animals do not seem to be capable of developing an acute tolerance to propofol. The results also support previous findings that a redistribution is important for the rapid clearance of propofol from blood.
Serum protein binding of propofol in patients with renal failure or hepatic cirrhosis
Authors: Costela J. L. , Jiḿenez R. , Calvo R. , Suarez E. , Carlos R.
Published: January 2009

Background:Serum protein binding is a limiting factor in the access of drugs to the central nervous system. Disease‐induced modifications of the degree of binding may influence the effect of anesthetic drugs.

Methods:The protein binding of propofol, an intravenous anaesthetic agent which is highly bound to serum albumin, has been investigated in serum samples from healthy volunteers, from patients with chronic renal failure not undergoing hemodialysis, from patients with chronic renal failure included in a regular hemodialysis program, and from patients with hepatic cirrhosis. Protein binding was determined by the ultrafiltration technique using an Amicon Micropartition System, MPS‐1.

Results:The percentage of unbound propofol (mean(SD)) in healthy volunteers (n=16) was 0.98 (0.48) % showing a high interindividual variability. Chronic renal failure did not significantly modify serum protein binding of propofol. In the chronic renal failure group not undergoing regular hemodialysis (n=>9), unbound propofol was 0.92 (0.34) %. In addition, patients in periodic dialysis did not show changes in propofol binding either compared before (1.11 (0.33) %; n=13) or after hemodialysis (0.87 (0.38) %; n=12). A slight decrease in albumin concentration was found in all renal patients (P<0.05) in comparison to healthy volunteers. Creatinine and urea concentrations were higher in these patients (P<0.01) but in the postdialysis group, the differences in urea levels were not significant when compared with those of volunteers. No changes in the degree of propofol binding were observed in patients with hepatic cirrhosis (0.97 (0.30) %; n=14) when compared with the group of healthy volunteers. Significant differences were observed in albumin (P<0.01) and bilirubin (P<0.05) concentrations. Considering all subjects, the degree of binding did not correlate with biomedical data.

Conclusion:Due to the the absence of significant changes in the protein binding it is unlikely that there will be an exaggerated pharmacological response in patients with renal and hepatic disease following the administration of a standard propofol dose, although due to interpatient variability careful titration can be recommended.
The efficacy of clonidine for reducing perioperative haemodynamic changes and volatile anaesthetic requirements in children
Authors: Nishina K. , Mikawa K. , Maekawa N. , Obara H.
Published: January 2009

Background: Oral clonidine given as a premedicant in adults has been shown to reduce intraoperative inhalation anaesthetic requirements and provide perioperative haemodynamic stability. We conducted the current study to ascertain whether or not these beneficial effects of clonidine can be reproduced in children.

Methods: In a prospective, randomized, double‐blind, controlled clinical trial, 60 children (ASA I) aged 5–11 yr, received placebo (control), 2 μg kg‐1 clonidine, or 4 μg kg‐1 clonidine orally 105 min before induction of anaesthesia. Anaesthesia was induced with halothane, nitrous oxide in oxygen via mask and maintained with halothane and 60% nitrous oxide in oxygen. The halothane concentration was titrated to the concentration required to maintain haemodynamic stability (defined as 20% of blood pressure (BP) and heart rate (HR)) for maintenance of anaesthesia. The end‐tidal concentration of halothane was monitored throughout anaesthesia. On completion of surgery, nitrous oxide and halothane were discontinued. Following confirmation of recovery from anaesthesia and muscle relaxation, the endotracheal tube was removed.

Results: Higher inspired concentrations of halothane (%) were required in the control and 2 μg kg‐1 clonidine‐treated groups (mean SD: 1.1 ±0.2 and 1.0±0.2, respectively) than in the 4 μg kg‐1 clonidine‐treated group (0.6±0.1) for haemodynamic stability (P<0.05). Clonidine, 4 μg kg‐1, significantly reuced the intraoperative lability (coefficient of variation) of systolic and diastolic BP and HR compared with the other two regimens.

Conclusion: Oral clonidine premedication at a dose of 4 μg kg‐1 provided intraoperative haemodynamic stability and reduced anaesthetic requirements in children. However, we are unable to extrapolate these observations to younger children and infants.
The interaction between nitrous oxide and isoflurane on suppression of learning: a study using classical conditioning in rabbits
Authors: El‐Zahaby H. M. , Ghoneim M. M. , Block R. I.
Published: January 2009

Background:Nitrous oxide (N2O) is commonly combined with a volatile agent for administration of general anesthesia. We studied the effects of N2O and isoflurane on learning of the rabbit nictitating membrane responses (NMRs).

Methods:Classical conditioning of the NMR was accomplished by presenting a 400 ms tone conditioned stimulus before the presentation of a 100 ms shock unconditioned stimulus over 6 daily training sessions. The percentages of conditioned responses (CRs) were calculated for animals treated with 0% (n=10), 33% (n=11), 67% (n=11), and 75% (n=7) N2O and for those treated with 0% (n=8), 0.2% (n=7), 0.4%, (n=13) and 0.8% (n=9) isoflurane separately. ED‐50 for suppression of learning for each drug were calculated. Percentages of CRs were calculated for treatments with combinations of 0.2% isoflurane with either 32 or 48% N2O (n=14, for each).

Results:Isobolographic analysis demonstrated that the combination of the two drugs exerted no greater effect than that seen with either agent administered alone; for well‐established CRs (mean of days 5 and 6), the estimated concentrations corresponding to a rate of 70% CRs were 0.31% isoflurane with no N2O, 65.3% N2O with no isoflurane, and 0.2% isoflurane combined with 32.4% N2O.

Conclusions:N2O and isoflurane interact additively on suppression of learning.
Comparison of the respiratory and systemic kinetics of nitrous oxide in the sheep
Authors: Reid M. A. , Mather L. E. , Isley A. H. , Runciman W. B.
Published: January 2009

Background. To determine whether discrepancies in views on the kinetics of nitrous oxide (N2O) may have a methodological basis, we compared its kinetics, simultaneously, in the respiratory system and systemic circulation.

Methods. Six merino ewes (40–50 Kg) were previously prepared with catheters in the pulmonary artery and aorta. The animals were anaesthetised with thiopentone then ventilated on a mixture of 70% N2O, 1% halothane in oxygen for 4 h. Simultaneous serial arterial and pulmonary arterial blood samples were assayed for N2O by gas chromatography and respiratory gases were monitored continuously by mass spectrometry.

Results. Marked differences were observed between the respiratory and systemic kinetics of N2O uptake. While the expired/inspired N2O concentration ratio rose within 30 min to a value close to unity, the pulmonary arterial/arterial blood N2O concentration ratio did not reach unity during the 4 h of each study, but approached a constant rate of uptake shown by the mean ratio of 0.94 (SD 0.01) from about 2 h onward.

Conclusions. Discrepancies in fluid flow between respiratory gas and the cardiovascular systems, a concentration effect of N2O in the lungs, the relative solubility of N2O in blood and tissues, and ventilation/perfusion inequalities all may contribute to the observed differences. The ongoing uptake is consistent with persistent extrapulmonary losses. There remains a need for experimental data on the pharmacokinetics of N2O. Unequivocal studies on the disposition of N2O can be undertaken only by using direct measurement of fluxes of N2O across relevant organs or tissues.
Dextran 70 and blood loss during transurethral resection of the prostate
Authors: Hahn R. G.
Published: January 2009

Background: Dextran is an effective plasma expander but also a potential anticoagulant. This article attempts to establish the clinical significance of any increased intra‐operative blood loss associated with the use of dextran 70 during transurethral resection of the prostate (TURP).

Methods: The blood loss was measured in used irrigating fluid by a photometer in 800 patients undergoing TURP. In 154 of them, 500‐1,000 ml of 6% dextran 70 was given for volume replacement. A regression model was used to test for interactions between the use of dextran and the operative parameters that correlated independently with the blood loss.

Results: The bleeding varied between 10 and 3,825 ml (median 323). Operative parameters correlating to the blood loss were: weight of the prostatic resectate, operating time, irrigating fluid absorption, and systolic arterial blood pressure. The result of this regression analysis indicated that dextran did not increase the blood loss. Neither did the prostatic weight and operating‐time‐corrected blood loss increase when dextran was infused.

Conclusion: There was no indication that dextran 70 given within the recommended dose range increases the blood loss during TURP.
Management of postoperative pain. An intervention study
Authors: Juhl I. U. , BÜlow H.‐H. , Nielsen P. R. , VidebÆk B. , Sonnenschein C.
Published: January 2009

Background: In 1989 a study had shown that the quality of postoperative pain treatment (PPT) in a district general hospital was not satisfactory. Therefore, new instructions for PPT were issued, intra‐venous medication with morphine was introduced on the wards, and the staff was educated in PPT. The purpose of this study was to investigate the quality of PPT in 1992 compared to the quality in 1989.

Methods: Using identical questionnaires, 191 patients in 1989 and 126 patients in 1992 were interviewed before and 2–5 days after surgery regarding postoperative pain. At the postoperative interview patients in pain also filled out the McGill Pain Questionnaire. A questionnaire was also answered by the nurses regarding PPT in 1989 and in 1992.

Results: 1992 compared to 1989 (1992/1989): all patients were now medicated (100%/93%), most of them regularly (79%/4%) and the majority (94%/15%) also received non‐opioid analgesic. Fewer patients (65%/80%) experienced postoperative pain lasting more than one day following surgery. Analgesic prescription was more standardized.

In 1992 the nurses were more satisfied than in 1989 with the PPT and the physicians' prescribing patterns.

All the above‐mentioned parameters were significantly improved from 1989 to 1992.

All the different pain‐scores showed a reduction (8–30%) but did not reach statistical significance (P=0.2).

Conclusions: Our two investigations show that it is possible to improve the quality of pain management with rather simple reforms.
Extradural abscess complicating lumbar extradural anaesthesia and analgesia in an obstetric patient
Authors: Kindler C. , Seeberger M. , Siegemund M. , Schneider M.
Published: January 2009

A 33‐year‐old nulliparous woman with severe pre‐eclampsia was treated with extradural analgesia to control blood pressure and relieve pain during delivery. Nine hours after extradural catheter insertion a Caesarean section was performed due to uterine inertia. The extradural catheter was kept in place for 88 hours. Ten days following the extradural block she developed an extradural abscess and had to undergo a laminectomy. In a retrospective and, in part, prospective analysis on more than 13,000 extradural blocks, we studied the incidence of this dreaded complication and reviewed the literature on clinical findings, diagnosis and treatment.
Anaesthesia and systemic oxygenation
Authors: Bacher A. , Mayer N. , Mittlboeck M. , Zadrobilek E.
Published: January 2009

Background: Anaesthesia induction and deep anaesthesia may be accompanied by a considerable haemodynamic depression, especially in patients suffering from cardiovascular diseases. A decrease in cardiac index (CI) leads to a concomitant decrease in oxygen transport (DO2I). We examined whether these changes in haemodynamic performance and oxygenation can cause an oxygen debt and anaerobic metabolism.

Methods: DO2I, oxygen uptake (VO2I), oxygen extraction ratio (O2ER) and plasma lactate were analysed at 9 pre‐defined study stages during anesthesia induction, deep anaesthesia prior to surgery and during surgery in 65 patients (ASA 3) undergoing elective vascular surgery. Polynomials of increasing order were fitted to the data for the determination of the critical value of oxygen transport from the inflection point of the regression curve.

Results: CI, heart rate, mean arterial pressure and DO2I decreased significantly after anaesthesia induction and during deep anaesthesia. VO2I showed an almost parallel change during the study period so that O2ER remained nearly constant. Plasma lactate did not exceed the physiological range in any patient and a critical value of DO2I could not be detected because a linear regression always provided the best fit for the data.

Conclusions: We conclude that in patients suffering from a substantial cardiovascular disease systemic oxygenation is not impaired by considerable haemodynamic changes induced by general anaesthesia. This fact can be explained by the parallel decrease in oxygen demand, expressed by the decrease in VO2I.
The combination of morphine with local anaesthetic in rhinoplasty ‐ no evidence of a peripheral morphine effect
Authors: Ben‐David B. , Moscona R. A. , Stahl S.
Published: January 2009

Background:The recognition of a peripheral opioid action has prompted a number of clinical reports demonstrating a prolonged analgesic effect of peripheral opiate. As most studies have used a model of intraarticular instillation of narcotic we examined direct morphine infiltration of the surgical site in a unique clinical model.

Methods:Sixty patients undergoing primary rhinoplasty were entered into this prospective, randomized, double‐blind study. Patients received a standard protocol of premedication, intravenous sedation, and nasal block. Two 2 ml syringes containing saline or morphine 3 mg in saline were provided for IM injection and for addition to the local anesthetic (IW, intrawound): Group I (control) ‐ saline IW, saline IM; Group II ‐morphine IW, saline IM; Group III ‐ saline IW, morphine IM. Intraoperative assessments included need for further sedation, need for further local anesthetic, and degree of bleeding. Recovery room analgesic requirements, pain scores, and recall of intraoperative pain were recorded prior to discharge. Followup phone calls at 24 hours recorded home pain scores and analgesic use during the first postoperative day.

Results:Significantly more patients in Group II (9/20) required supplemental local anesthetic intraoperatively compared to Group I (2/20) and Group III (0/20). Significantly more patients in Group II (6/20) recalled their surgical experience as painful compared to Group I (1/20) and Group III (1/20). Group II patients also evidenced significantly more operative bleeding. There were no differences in postoperative pain scores, but Group I patients required analgesic in the recovery room significantly more than in Groups II and III (85%vs45% and 50%, respectively). There were no differences between groups in analgesic consumption at home.

Conclusions:The results of this study indicate that the preoperative injection of intrawound morphine in combination with the local anesthetic both promotes bleeding and has an early pain‐enhancing effect while providing no late analgesic benefit beyond that of IM morphine.
Pharmacokinetics of piritramide after an intravenous bolus in surgical patients
Authors: Kietzmann D. , Briede I. , Bouillon T. , Gundert‐Remy U. , Kettler D.
Published: January 2009

Background: Piritramide is a synthetic opioid analgesic which is commonly used for postoperative analgesia. It is structurally related to meperidine, exhibiting full μ‐receptor agonism. Pharmacokinetic data of the drug have not been reported so far.

Methods: Plasma protein binding of piritramide was studied in vitro. The kinetics were examined after a single intravenous bolus (0.2 mg/kg) in 10 male patients aged 22–53 years undergoing elective minor surgery. Plasma and urine concentrations were determined by gas chromatography in samples drawn before and after the bolus. The concentration vs. time data were evaluated by nonlinear regression analysis, and the mean values and SD of the individual pharmacokinetic parameters were calculated. A three‐compartment body model was fitted to the data.

Results: The volume of distribution at steady state was 4.7 (0.7) 1/kg, systemic plasma clearance was 7.8 (1.5) (mean (SD)) ml/kg/min. Renal clearance of unchanged piritramide was negligible (0.13 (0.09) ml/kg/min). The terminal elimination half‐life was 8.0 (1.4) h. In vitro, the free fraction in plasma of piritramide did not change over the therapeutic concentration range (5.5 (1.3)% at a pH of 7.35) but decreased considerably with pH within the physiological range.

Conclusion: Since the elimination half‐life of piritramide appears to exceed the duration of clinically effective analgesia observed during the treatment of acute pain, the dose of piritramide should be titrated carefully during long‐term treatment to avoid accumulation that may lead to adverse effects.
Age and life‐sustaining treatment Attitudes of intensive care unit professionals
Authors: Melltorp G. , Nilstun T.
Published: January 2009

Background: In Sweden, the official policy is that life‐sustaining treatment should not be denied because of chronological age. This policy is also emphasised in a recent official report on priority setting in health care. But is this policy accepted among health care professionals? Do they consider chronological age relevant when decisions to forgo life‐sustaining treatment are to be made?

Method: Questionnaire survey to physicians, registered nurses and enrolled nurses at the Intensive Care Unit, University Hospital MAS, Malmö, Sweden.

Results: More than 65% of the respondents were of the opinion that chronological age per se influenced decisions about life‐sustaining treatment. Fewer, a little more than 40%, answered that it would make a difference to their own judgment about life‐sustaining treatment whether the patient is 25 or 75 years old. The respondents were also confronted with 10 different factors characterising patients in need of life‐sustaining treatment. According to a majority, advance directive, decision‐making capacity, and chronological age should be taken into consideration in these situations.

Conclusion: The results indicate that chronological age is used as a criterion when decisions to forgo life‐sustaining treatment are to be made in the ICU. Many health care professionals also believe that chronological age should be used as a criterion. This is clearly discordant with the official policy in Sweden and other countries, which is that age‐based rationing is never justified.
Hemodynamic effects of tracheal and intravenous adrenaline in infants with congenital heart anomalies
Authors: Jonmarker C. , Olsson A.‐K. , Jögi P. , Forsell C.
Published: January 2009

Background: If intravenous access cannot be accomplished during cardiopulmonary resuscitation in children, tracheal administration of 100 μg/kg of adrenaline (ten times greater than the intravenous dose) is recommended.

Methods: In a randomized crossover study we recorded the hemodynamic effect of a low dose of intravenous adrenaline and a ten times greater tracheal dose. While anesthetized for open heart surgery, fourteen infants received one dose of adrenaline intravenously (0.3 μg/kg) and the other tracheally (3μg/kg).

Results: During the first 5 minutes after administration mean arterial pressure (MAP) and heart rate (HR) increased after both intravenous and tracheal administration (P<0.001). The maximum increase in MAP was 28% (17–68%, median and range) after intravenous injection and 20% (6–69%, P<0.05 when compared to intravenous injection) after tracheal instillation. In four infants, MAP increased less than 10% after tracheal instillation. The maximum increases in MAP and HR occurred 1 min (1–2 min) after intravenous injection and 3 min (2–4 min) after tracheal instillation (P<0.001).

Conclusion: Tracheal administration of 3 μg/kg adrenaline increased mean arterial blood pressure in infants with congenital cardiac anomalies, but the increase occurred later and was less consistent than after 0.3 μg/kg of adrenaline given intravenously.
A paediatric canopy system for aerosol administration and minimized environmental pollution
Authors: WÅhlin B. , Malmström B. , Soop M. , Hellströ;m L.‐G.
Published: January 2009

Background: A canopy system for ribavirin aerosol administration to infants has been developed in order to improve the control of aerosol treatment, facilitate access to the infant and minimize environmental pollution. The system comprises a transparent canopy, fitted with four sealable apertures. An evacuation flow that is 3 1/min higher than the gas supply was anticipated to prevent aerosol leakage from the canopy.

Method: In a clinical evaluation, 10 infants with body weights of 1.8‐7.1 kg were placed inside the canopy during 1 hour of simulated treatment. The temperature, relative humidity and carbon dioxide concentration within the canopy were measured repeatedly to study the stability of these variables and their dependence on body weight. Infant body temperature, skin temperature and the respiratory frequency were measured. In a laboratory evaluation, aerosol leakage was studied using an ambient air admixture procedure and smoke tests. The sound level inside the canopy was measured.

Results: All physical variables inside the canopy remained stable. The sound level was 52 dBA. The carbon dioxide concentration (1000–3900 PPM) correlated with infant body weight (P<0.001), as did canopy temperature (25.1–29.6°C, P<0.05). The relative humidity was 52–88%. Infant body temperatures were not influenced. The respiratory frequency decreased by 13% (P<0.01). No aerosol leakage was observed. Conclusion: The canopy system facilitates a controlled aerosol therapy with good infant surveillance and accessibility, a minimum of environmental pollution and a comfortable physical environment without apparent risks of carbon dioxide rebreathing or cooling stress at body weights of 1.8‐7.1 kg.
High energy phosphates and direct calorimetry as predictive parameters for metabolic recovery of the rat liver following ischemia
Authors: Bach F. , Singer D. , Schmiedl A. , Bauer M. , Larsen R.
Published: January 2009

Backround and Methods: Alteration of the hepatocellular function following ischemic damage may play a crucial role in the limited recovery after reperfusion. In spite of numerous efforts, finding a simple technique for predicting recovery of the liver after ischemic damage is still an unresolved problem. During ischemic storage of isolated rat livers at 25°C tissue concentrations of high energy phosphates and lactate were determined photometrically and interstitial pH was measured by glass electrodes. In comparison, the metabolic rate was measured continuously by direct calorimetry. In a second series of experiments these results were compared with functional recovery after ischemia and reperfusion. Following ischemic storage at 25°C for 60, 120 or 240 min, the isolated livers were reperfused for 30 min in a non‐recirculating system with a constant flow rate. During reperfusion functional recovery, as assessed by oxygen consumption and bile flow, was determined. At the end of reperfusion tissue samples were taken for biochemical analysis of adenine nucleotides. Furthermore, morphologic integrity was determined by electron microscopy.

Results: Whereas the ATP concentration drops within 60 min of ischemia to 6.9% of the control value without further significant change, the continuously measured metabolic rate as assessed by direct calorimetry decreases in an exponential manner. Accordingly, a better correlation of hepatocellular secretory function and calorimetrically measured heat output (r2=0.85; P<0.001) was observed than with high energy phosphates (r2=0.56; P<0.001).

Conclusions: These data suggest that if the metabolism of the ischemic rat liver falls below a critical level, recovery is incomplete or impossible. Therefore, assessment of the global metabolic rate by direct calorimetry seems not only to be a very good predictor of recovery after ischemic damage but also a good tool in the laboratory for studies concerning the sequelae of ischemic metabolism and for improvement of tissue protection.
Sequestration of vecuronium bromide during extremity surgery involving use of a pneumatic tourniquet
Authors: BARNETTE R. E. , ERIKSSON L. I. , COONEY G. F. , BRISTER N. W. , JOHANSON N. , CARLSSON C. , SHARMA M. L.
Published: January 2009

Background: We hypothesized that sequestration of a neuromuscular blocking agent could occur during surgery involving use of an extremity tourniquet and cause changes in neuromuscular function after tourniquet release.

Methods: Sixteen patients scheduled for total knee replacement were randomized to one of two groups. In Group 1,10 patients were administered O.lmg/kg of vecuronium 5 minutes prior to inflation of a pneumatic tourniquet; in Group II, 6 patients were administered O.lmg/kg of vecuronium after inflation of the tourniquet. The twitch (T1) and train‐of‐four (TOF) were analyzed before and after release of the tourniquet, as was the rate of recovery of T1 and TOF. Serial vecuronium plasma levels were drawn during the study.

Results: The T1 and TOF responses and the T1 and TOF recovery rates were not significantly different between groups at tourniquet deflation. In Group I, after release of the tourniquet, Tj and TOF recovery rate decreased significantly over a 10‐min period (10%±3 to 4%±4 and 0.12±0.06 to 0.06±0.04, mean±SD, respectively); in Group II, T1 and TOF recovery rate increased significantly over a 10‐min period following deflation of the tourniquet (10%±6 to 14%±7 and 0.10±0.03 to 0.18±0.02, respectively). Changes in pharmacodynamics were temporally associated with transient but statistically significant changes in vecuronium plasma levels. Overall pharmacokinetics during the study period were comparable between groups. After administration of neostigmine 30–40 μg/ kg i.v. all subjects in both groups showed complete TOF recovery within 15 min.

Conclusions: Sequestration of a bolus dose of vecuronium, by a pneumatic tourniquet, causes transient changes in pharmacokinetics and pharmacodynamics. These changes are of limited clinical importance and do not affect reversibility of neuromuscular block.
Hyperosmotic‐hyperoncotic solutions during abdominal aortic aneurysm (AAA) resection
Authors: CHRIST F. , NIKLAS M. , KREIMEIER U. , LAUTERJUNG L. , PETER K. , MESSMER K.
Published: January 2009

A largely positive perioperative fluid balance during both elective and emergency abdominal aortic aneurysm repair (AAA) may put patients at risk of developing left ventricular failure and may thus contribute to morbidity. In the present paper we report on a prospective study using hyperosmotic‐hyperoncotic solutions (HHS) infused during clamping of the aorta, for the prevention of declamping shock, and the associated reduction in perioperative fluid requirements. The major aim of this paper was to determine the efficacy of an HHS infusion when given over 20 minutes and to detect possible adverse effects of HHS.

For perioperative fluid replacement 12 patients received crystalloid solutions with HHS [250 ml of 7.2% NaCl combined with either 6% Dextran (n=3), 6% Hydroxyethylstarch (HES, n=4) or 10% HES (n=5)]. In 16 controls, crystalloids with 1000 ml of HES 10% were infused. Patients were invasively monitored and hemodynamic parameters frequently assessed during the operation, which were statistically analyzed in relation to the start of the fluid loading during clamping of the aorta. One patient showed an anaphylactoid reaction to HES, otherwise no side effects of HHS were observed during infusion (no hypotension, no pathological EKG changes). Plasma sodium and chloride concentration as well as osmolality rose resulting in an osmotic gradient and a desired intravascular volume expansion. Prior to declamping pulmonary capillary wedge pressure had increased to the desired value of > 13 mmHg and <18 mmHg. Oxygen delivery was significantly elevated upon HHS and remained so post declamping, whereas no change was observed in controls. During clamping systemic vascular resistance was significantly decreased, but was unchanged in controls. The perioperative fluid balance of patients receiving HHS was 2471.0±948.6 ml, which was significantly less than +3386.7±1247.9 ml of controls (P < 0.01).

We suggest that HHS opens new perspectives in perioperative fluid management of both elective and emergency AAA repair, since hemodynamic parameters are improved and the overall fluid balance is less positive, thus decreasing the likelihood of edema formation. Moreover, the previously described positive microcirculatory effects of HHS may be particular beneficial in some high‐risk patients.
Pharmacology and mechanisms of opioid analgesic activity
Authors: YAKSH T. L.
Published: January 2009

Opiates by an action at specific receptors can induce a highly selective alteration in the response of humans and animals to strong and otherwise aversive chemical, mechanical or thermal stimuli. Specific investigations in a variety of species from rodent to primate using microinjection techniques to examine the pharmacology of local drug action have shown potent antinociceptive actions to be mediated by a receptor specific action at a number of sites within the brain, including the periaqueductal gray (PAG: μ receptor), the rostral ventral medulla (μ/δ receptor) and the substantia nigra (μ receptor) and within the spinal dorsal horn (μ/δ/K receptor). Mechanistic studies have shown these actions in the different sites to be mediated by several discrete mechanisms. For example, in the PAG, the local opiate effect is likely mediated by the indirect activation of bulbospinal pathways, rostral projections to forebrain sites and by a local alteration in afferent input into the brainstem core. In the spinal cord, this effect is mediated by an action presynaptic to the primary afferent and by a post‐synaptic effect to hyperpolarize projection neurons. In addition, it is now appreciated that μ and K receptors in the periphery can modulate the sensitized state of the small afferent terminal innnervating inflamed tissue and exert an anti‐hyperalgesic action. After systemic delivery of an opiate, it is thus clear that a wide array of central and peripheral systems serve to explain the powerful analgesic effect exerted by this class of agents.
Morphine metabolites
Authors: CHRISTRUP L. L.
Published: January 2009

Morphine is a potent opioid analgesic widely used for the treatment of acute pain and for long‐term treatment of severe pain. Morphine is a member of the morphinan‐framed alkaloids, which are present in the poppy plant. The drug is soluble in water, but its solubility in lipids is poor.

In man, morphine‐3‐glucuronide (M3G) and morphine‐6‐glucu‐ronide (M6G) are the major metabolites of morphine. The metabolism of morphine occurs not only in the liver, but may also take place in the brain and the kidneys. The glucuronides are mainly eliminated via bile and urine. Glucuronides as a rule are considered as highly polar metabolites unable to cross the blood‐brain barrier. Although morphine glucuronidation has been demonstrated in human brain tissue, the capacity is very low compared to that of the liver, indicating that the M3G and M6G concentrations observed in the cerebrospinal fluid (CSF) after systemic administration reflect hepatic metabolism of morphine and that the morphine glucuronides, despite their high polarity, can penetrate into the brain. Like morphine, M6G has been shown to be relatively more selective for μ‐receptors than for 5‐ and K‐receptors while M3G does not appear to compete for opioid receptor binding.

The analgesic properties of M6G were recognised in the early 1970s and more recent work suggests that M6G might significantly contribute to the opioid analgesia after administration of morphine. The analgesic potency of M6G after intracerebroven‐tricular (ICV) or intrathecal (IT) administration in rats is from 45–800 timer greater than that of morphine, depending on the animal species and the experimental antinociceptive test used. Furthermore, the development of a sensitive high‐performance liquid chromatography (HPLC) assay for the quantitative determination of morphine, M6G and M3G has revealed that M6G and M3G were present in abundance after chronic oral morphine administration and that the area under the plasma concentration‐time curve exceeded that of morphine. M3G has been found to antagonise morphine and M6G induced analgesia and ventilatory depression in the rat, which has led to the hypothesis that M3G may influence the development of morphine tolerance. M3G exhibits no analgesic effect after ICV or IT administration. Some studies do, however, indicate that M3G may cause non‐opioid mediated hyperalgesia/allodynia and convulsions after IT administration in rats. These observations led to the hypothesis that M3G might be responsible for side‐effects, hyperalgesia/allodynia and myoclonus seen after high‐dose morphine treatment.