bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
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.
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.
Decisions not to resuscitate in a Swedish university hospital
Authors: FRIBERG H. , ADOLFSSON A. , LUNDBERG D. 
Published: January 2009

Background: Cardiopulmonary resuscitation (CPR) has the potential to save many lives. Used indiscriminately though, it may be harmful and not in the best interest of the patient. An advance directive to refrain from resuscitation in selected patients is probably not uncommon in Sweden, but guidelines ruling this are still generally lacking. This study was performed to evaluate the use and documentation of do–not–resuscitate orders in a Swedish university hospital.Methods: Adult inpatients at 7 medical, 3 surgical and 2 neurological wards, a total of 220, were investigated on one specific day by interviewing the physicians and nurses responsible for their care.Results: We found a discrepancy in doctors' and nurses' perception concerning the appropriateness of CPR in selected patients. CPR was judged by doctors to be inappropriate for 45 patients (20%). Out of these 45 patients, only 24 had a written do–not resuscitate order in their medical record, in most cases noted as a code word or sign only. Rarely were the patient or his/her relatives involved in the decision–making process.Conclusion: We conclude that a decision to refrain from resuscitation is often not made, even when considered medically and ethically justifiable. Also, the use of coded information as a sole indicator for a patient not to be resuscitated is still common practice. The patient or his/her relatives are rarely involved in this decision.
Serum protein binding of propofol in critically ill patients
Authors: ZAMACONA M. K. , SUÁREZ E. , AGUILERA L. , RODRÍGUEZ–SASIAÍN J. M. , AGUIRRE C. , CALVO R. 
Published: January 2009

Background: Disease‐induced modifications in the level of serum proteins may change the degree of binding of drugs highly bound to serum proteins.Methods: The serum protein binding of propofol, an intravenous anaesthetic agent, was studiedin vitroin samples of serum from healthy volunteers (n = 28) and from critically ill patients (n = 17). The free fraction was obtained by the ultrafiltration technique and was measured by high‐performance liquid chromatography. Concentrations of serum albumin, α1acid‐glycoprotein and free fatty acids were also measured in all samples.Results: The percentage of free propofol was significantly increased (P< 0.001) in critically ill patients (1.31 (1.06–2.25)%) vs control subjects (1.07 (0.49–1.47)%). Albumin levels were significantly decreased (P<0.001) in patients (16.3 (8.8–24.6) g–1‐1vs 45.8 (31.4–55.5) g–1“1), while levels of α1‐acid‐glycoprotein were increased (P<0.001) (1.9 (0.9–2.8) g l‐1vs 0.9 (0.5–1.4) g 1‐1), as were levels of free fatty acids (0.68 (0.50–1.14) mmol I‐1vs 0.37 (0.11–1.05) mmol I‐1;P< 0.05). No correlation was found between levels of α1–acid–glycoprotein or free fatty acids and the bound/free ratio of propofol. However, a linear relationship was found between levels of albumin and the bound/free ratio (r2=O.25;P< 0.001).Conclusion: In conclusion, in these critically ill patients, an increase in the percentage of free propofol occurs. The significance of this observation remains uncertain, but may be validated in future studies. However, the observation supports the common idea that potent drugs should be given with great care in critically ill patients.
Comparison of ondansetron and droperidol in the prevention of postoperative nausea and vomiting after laparoscopic surgery in women
Authors: KOIVURANTA M. , LÄÄRÄ E. , RANTA P. , RAVASKA P. , ALAHUHTA S. 
Published: January 2009

Background: Women undergoing laparoscopic surgery are susceptible to postoperative nausea and vomiting (PONV). Ondansetron and droperidol are useful antiemetics. This study was designed to ascertain primarily the relative difference in efficacy of ondansetron and droperidol and secondarily between these drugs and placebo in the prevention of PONV after laparoscopic surgery.Methods: The prophylactic antiemetic efficacy of ondansetron and droperidol was compared in a prospective, randomised, double–blind, placebo–controlled trial of 439 female inpatients scheduled for laparoscopic surgery. During induction of standardised general anaesthesia the patients received intravenously either ondansetron 8 mg (n=195), droperidol 1.25 mg (n=193) or placebo (n=51). The occurrence of nausea, vomiting, sideeffects and the need for rescue antiemetic medication were recorded for 24 h postoperatively.Results: The proportion of patients with nausea was 48%, 50% and 67% in the ondansetron, droperidol and placebo groups, respectively; with a significant difference when both ondansetron (P=0.02) and droperidol (P=0.04) were compared with placebo. Vomiting occurred in 18%, 26% and 37% of the patients in the three groups, respectively (P=0.05 between ondansetron and droperidol, P=0.004 between ondansetron and placebo, P=0.16 between droperidol and placebo). The proportion of patients given rescue medication was 34%, 28% and 49%, respectively (P=0.23 for ondansetron and droperidol, P=0.07 for ondansetron and placebo, P=0.007 for droperidol and placebo). During early recovery the patients treated with ondansetron were significantly more alert than after droperidol. Serious side–effects were not observed. Headache was significantly more common after ondansetron than after droperidol treatment.Conclusions: The efficacy of prophylactic ondansetron and droperidol in reducing postoperative nausea associated with laparoscopic surgery in female inpatients was similar, but ondansetron appeared to be slightly more efficient than droperidol in preventing vomiting. Ondansetron and droperidol were both significantly better than placebo in the prophylaxis of PONV.
Treatment of ventricular fibrillation during anaesthesia in an anaesthesia simulator
Authors: LINDEKÆR A. L. , JACOBSEN J. , ANDERSEN G. , LAUB M. , JENSEN P. F. 
Published: January 2009

Background: To evaluate treatment of ventricular fibrillation (VF) occurring during anaesthesia and the use of a full–scale simulator, 80 anaesthetists in teams of two were attending a training session in the simulator Sophus.Methods: The sessions were recorded on videotape and reviewed with the anaesthetists afterwards. Time of treatment and the sequence were registered.Results: Onset time for VF was the starting point. Most of the subjects changed respiratory settings. Four teams did not change inspiratory oxygen and 17 teams did not turn off the vaporiser. Cardiac compression was initiated by all teams. DCdefibrillation was not used by two teams, with 38 of 40 teams defibrillating once, 37 twice and 29 teams three times. Adrenaline was administered by 30 of 40 teams.Conclusion: There was very little consistency among the teams regarding treatment for VF according to accepted algorithms. An anaesthesia simulator could be a tool for training and it is a safe way of demonstrating for the anaesthetist that certain treatment algorithms and behaviour during critical incidents are the most effective.
Should nitrous oxide be discontinued before desflurane after anaesthesia with desflurane/N2O?
Authors: EINARSSON S. , CERNE A. , BENGTSSON A. , STENQVIST O. , BENGTSON J. P. 
Published: January 2009

Background: The appearance of hypoxaemia immediately after anaesthesia with nitrous oxide may be partially explained by diffusion hypoxia. This study was undertaken to evaluate circulatory and respiratory variables during emergence after desflurane/nitrous oxide anaesthesia, and whether there are any differences depending on which gas is discontinued first.Methods: 20 patients were studied after gynaecological laparoscopic surgery. The depth of anaesthesia was reduced 10 min prior to the emergence by stopping the administration of one of the two inhalational agents. Desflurane was discontinued first in Group 1, nitrous oxide in Group 2. Ventilation was controlled with E'C02 maintained at 5% until the administration of the second anaesthetic gas was discontinued. Thereafter, the patients breathed spontaneously.Results: The PaC02 at which the respiratory drive reappeared after controlled normoventilation was similar in both groups, 6.1–6.5 kPa, and extubation was performed after 10–11 min. At extubarion, the end–tidal C02 and total MAC were similar in the groups, about 6.2 vol% and 0.16, respectively. Mean arterial blood pressure was significantly higher in Group 1. The cardiac output increased in both groups from about 6 1/min at the conclusion of anaesthesia to 9.0 and 7.6 1/min at 15 min in the recovery period. End–tidal O2 decreased and CO2 increased in both groups during the first 10 min in the recovery period. pH was reduced at 15 and 30 min in both groups.Conclusion: Irrespective of which agent was discontinued first, there was an increase in cardiac output, decrease in oxygenation and a modest acidosis in the first 30–min recovery period. The only significant difference between the groups was in mean arterial blood pressure in the early emergence phase with a greater MAP when N2O had been used until the conclusion of anaesthesia.