Urinary morphine excretion during and after morphine anaesthesia for open-heart surgery in children

The urine of 20 children undergoing complete correction of atrial septal defect (ASD) or tetralogy of Fallot (TF) were analyzed for morphine and its glucuronide conjugation product before and after induction of morphine anaesthesia, throughout the operation and for two hours post-operatively. Children with ASD had a higher, mean urine flow rate during anesthetic induction and during the entire operation than those with TF (P less than 0.01). ASD children excreted a greater percentage of the administered morphine by the time they reached the recovery room and after two hours in the recovery room than those with TF. Urinary morphine in the glucuronide form increased progressively from anaesthetic induction until the post-operative period in both groups and was more than 93% after two hours in the recovery room. Fifty-five per cent of ASD patients had respiratory dynamics that enabled them to be extubated within six hours of the end of their operation. Those that could be extubated after six hours had excreted a significantly greater percentage of morphine than those that couldn't (P less than 0.025). None of the children with TF could be extubated until the day after operation. These data demonstrate that the ability to maintain adequate spontaneous respiration after morphine anaesthesia is directly related to urinary output during anaesthesia and operation.     

Patient-maintained analgesia with target-controlled alfentanil infusion after cardiac surgery: a comparison with morphine PCA

Intuitively it seems obvious that unrelieved, severe acute pain after surgery may have a number of undesirable effects [1]. Many experienced clinicians maintain that the immediate postoperative course as well as long-term outcome may be influenced by the quality of pain relief after surgery or trauma [1, 2]. However, there are conflicting data from published clinical studies concerning the beneficial effects of postoperative pain management on short-term and long-term outcome of surgery [3].     

Comparison of morphine with and without fentanyl for epidural analgesia after major abdominal surgery

Expression of fusion proteins between prepro-alpha-factor and somatostatin (SRIF) in yeast, resulted in the correct processing and secretion of the heterologous 14-amino acid SRIF peptide (1). When the chimeric genes were placed under the control of yeast acid phosphatase (PHO5) promoter, significant amount of an unglycosylated form of the fusion precursor molecule accumulated intracellularly, suggesting disruption of an endoplasmic reticulum-mediated function. We report here that the appearance of the precursor is due to an alteration in the three amino terminal residues of the chimera, i.e., Met-Arg-Phe in native prepro-alpha-factor is changed to Met-Phe-Lys in the hybrids. The unglycosylated precursor represents a population of molecules that are disrupted at an early stage of targeting to or translocation across the endoplasmic reticulum membrane. Our data demonstrate that the N-terminus plays an important role in topogenesis. Furthermore, these results show that translocation and glycosylation can be uncoupled from protein synthesis in vivo, and therefore can be posttranslational events in yeast.     

Follow-up compliance in febrile children: a comparison of two systems

OBJECTIVES: Follow-up compliance is critical in febrile children because they may harbor unrecognized life-threatening illnesses. This study compares follow-up rates between 2 systems: Wilford Hall Medical Center (WHMC), with preset appointments after ED release, and free medical care; and Fairfax Hospital (FFX), where parents must arrange follow-up appointments after ED release, and are responsible for payment for their follow-up visits. The study also investigated factors associated with follow-up compliance. METHODS: This was a prospective, observational study of febrile children seen in 2 EDs with different systems for patient follow-up. From ED records and parental phone calls, diagnosis, follow-up compliance, and demographics were collected. Data were analyzed using logistic regression and chi2. RESULTS: 423 children met entrance criteria, and 330 parents were successfully contacted after the child's ED release (146 from WHMC; 184 from FFX). The WHMC children were more likely to comply with follow-up than were the children in the FFX system (92% vs 67% follow-up, odds ratio 2.5, 95% CI 1.1-5.3). Other factors associated with noncompliance with recommended follow-up were: Hispanic ethnicity, non-English-speaking parents, and follow-up suggested for >24 hours after ED release. For FFX, self-pay, lack of a follow-up physician, parents' dissatisfaction with the ED medical care, and diagnosis of otitis media were also significant factors found associated with noncompliance. CONCLUSION: Febrile children evaluated in a medical system with prearranged follow-up appointments and free medical care are more likely to comply with recommended follow-up than are those evaluated in a system where payment and appointments are the responsibility of the parents. Efforts should be made to improve follow-up compliance by modeling the WHMC system.     

Impaired recovery of strength in older patients after major abdominal surgery

OBJECTIVE: This study compared changes in muscle strength after major elective abdominal surgery in young and old patients, and related these changes to body composition and nitrogen balance. SUMMARY BACKGROUND DATA: The breakdown of muscle protein, erosion of lean tissue, and negative nitrogen balance are characteristic metabolic responses to surgical illness. With a substantial loss of muscle mass typical of advancing age, the authors postulated that older patients would be weaker during acute surgical illness and less able to maintain muscle function and meet metabolic demands. METHODS: Active, community-dwelling individuals undergoing major abdominal procedures who were 70 years of age or older or 50 years of age or younger were studied. Total body water (TBW) was determined preoperatively by deuterium oxide dilution. Maximal voluntary handgrip, respiratory muscle strength, and visual analog pain scores were measured preoperatively and on postoperative days 2, 4, and 6. All urine was collected postoperatively for 7 days for determination of total nitrogen, creatinine, and cortisol. RESULTS: The young (age, 36 +/- 9 years [mean +/- standard deviation]; n = 20) and old groups (age, 77 +/- 5 years; n = 20) were similar regarding weight, sex distribution, nutritional status, surgical procedures and anesthesia, and postoperative urine cortisol values. Age group, time after operation, and interaction effects were significant for each strength variable (all p < 0.005 by analysis of variance). Older patients had lower preoperative strength (29% to 41%) and mean 24-hour urine creatinine (27%). Postoperative strength was decreased most markedly on postoperative day 2, with similar proportional changes in the two age groups but lower absolute levels in the older patients. The rate of recovery of strength was substantially less rapid and complete in older patients. Older patients had less postoperative pain and received much less parenteral narcotic than younger patients. Postoperative urine nitrogen was similar in each group. Recovery of strength was not related to malignancy, preoperative strength, muscle mass (urine creatinine), lean body mass (TBW), sex, malignancy, pain, or narcotic administration. CONCLUSIONS: Older patients are weaker preoperatively than younger patients; their strength falls to lower levels after surgery and their postoperative recovery of strength is impaired. The lesser preoperative strength of older patients is due in large part but not totally to diminished muscle mass. Their impaired postoperative recovery appears to be related to more acute factors, such as muscle energetics or substrate availability.     

Postoperative analgesia with intramuscular morphine at fixed rate versus epidural morphine or sufentanil and bupivacaine in patients undergoing major abdominal surgery

Hydrofluoroalkane-134a (HFA) beclomethasone dipropionate (BDP) was formulated in a metered-dose inhaler (MDI) to deliver a particle size of 1.1 microm compared with 35 microns for currently marketed chlorofluorocarbon (CFC)-BDP products. Two phase I single-dose human deposition studies were conducted using technetium 99m-radiolabelled BDP in a press-and-breathe actuator without an add-on spacer. A healthy volunteer study (n=6) showed that 55-60% of the HFA-BDP ex-actuator dose was deposited in the lungs, with 29-30% deposited in the oropharynx. CFC-BDP deposition was 4-7% in the lungs and 90-94% in the oropharynx. The pattern of deposition within the lung showed that HFA-BDP was spread diffusely throughout the lung airways, whereas CFC-BDP was confined to the central airways with little, if any, peripheral airway deposition. A second study with asthmatics (n=16) confirmed that 56% of the HFA-BDP dose was deposited in the airways, with 33% in the oropharynx. In conclusion, hydrofluoroalkane-134a-beclomethasone dipropionate deposition was much greater in the airways than chlorofluorocarbon-beclomethasone dipropionate, with a concomitant reduction in oropharyngeal deposition. The increased lung deposition efficiency of the hydrofluoroalkane propellant has led to a reduction in the amount of beclomethasone dipropionate needed to achieve a similar efficacy. The penetration of the hydrofluoroalkane to the small airways may provide asthma treatment not afforded by conventional chlorofluorocarbons.     

Caudal and spinal anesthesia in sub-umbilical surgery in children. Apropos of 1875 cases

Caudal and spinal anaesthesia are two techniques widely used in European children. The aim of this retrospective study was to evaluate the applicability of this practice in developing countries. The study concerned 1875 children, 1 day to 17 years old. isobaric 0.5% bupivacaine was used for spinal anaesthesia (n = 730) and mixture a of 1% lidocaine-0.25% bupivacaine with epinephrine 1/200,000 for caudal anaesthesia (n = 1,145). Spinal anaesthesia was performed in neonates and infants (< 3 years) and caudal anaesthesia in children (aged 14 days to 17 years) undergoing urological and lower extremity surgery. No variation of heart rate, blood pressure or blood oxygen saturation (SpO2) were observed during surgery. Failure of the technique was less than 1%. These two regional anaesthesia techniques are easy to perform and are inexpensive. This is advantageous for developing countries.     

Central haemodynamic and forearm vascular effects of morphine in patients after open heart surgery

Central haemodynamic and forearm vascular changes following administration of morphine i.v. were studied in patients 24--30 h after open heart surgery. Right atrial pressure, heart rate, mean arterial pressure, cardiac output and stroke volume were measured before and after morphine 5 and 10 mg per 70 kg in 14 subjects. In a further group of eight subjects, forearm blood flow was measured after morphine 10 mg per 70 kg. Total systemic and forearm vascular resistance were derived from these measurements. In spite of wide individual variations, significant decreases in mean arterial pressure occurred in most of the patients and appeared to be dose related. Significant decreases in mean cardiac index were noted only after morphine 10 mg per 70 kg. Forearm blood flow increased consistently and significantly and there was a corresponding decrease in vascular resistance. The decrease in mean arterial pressure and the change in forearm vascular resistance indicated that vasodilatation was probably the principle cause of the decrease in arterial pressure, whereas the sustained decrease in cardiac output seemed to indicate an effect on venous capacitance. The predominant action of morphine appears to be peripheral, causing a decrease in vascular resistance and, possibly, an increase in venous capacitance.     

Respiratory effects of intravenous morphine infusions in neonates, infants, and children after cardiac surgery

We evaluated the respiratory effects of intravenous morphine infusions in 30 patients (2 to 570 days old, mean 155 days) after cardiac surgery. PaCO2 during spontaneous breathing and CO2 response curves during rebreathing were obtained on morphine infusions at drug steady state and during drug washout. Steady state morphine serum levels > 20 ng/mL resulted in hypercarbia (PaCO2 > 55 mm Hg) and depressed CO2 response curve slopes (< 10 mL.min-1.mm Hg ETCO2(-1).kg-1) in 67% and 70% of patients, respectively (P < 0.05, compared to those with levels < 20 ng/mL). During washout, morphine levels more than 15 ng/mL resulted in hypercarbia in 46%, whereas levels less than 15 ng/mL were associated with hypercarbia in 13% (P = 0.025). No age-related differences in respiratory effect were seen in these studies at the same serum morphine level. Careful observation of any patient receiving morphine remains necessary, but neonates and young infants seem to have the same respiratory response to morphine infusions as older infants and children at the same blood level.     

Apnoea and oximetric desaturation in patients receiving epidural morphine after gastrectomy: a comparison of intermittent bolus and patient controlled administration

The number of apnoeic episodes and arterial oxygen desaturations were measured preoperatively and for sixty hours postoperatively in twenty ASA status 1-2 patients scheduled for elective gastrectomy. Monitoring included continuous pulse oximetry, respiratory inductive plethysmography and repeated arterial blood gas analysis. The number and magnitude of apnoeas and desaturation episodes were compared between two postoperative analgesic regimens of epidural morphine; intermittent bolus injection (Group B, n = 10), and patient controlled administration with continuous infusion (Group P, n = 10). Morphine dose, P(a)CO2 and mean SpO2 values were similar between the two groups. Although the number of central apnoeas with SpO2 < 90% was greater in Group B, other episodes of apnoea or desaturation were similarly seen preoperatively. In the postoperative period, central apnoeas with SpO2 < 90% were significantly increased in Group B, while no change was seen in Group P. Apnoeas with SpO2 < 80% were only seen in Group B. We conclude from these results that postoperative apnoeas and episodic desaturations are greatly influenced by the different modes of opioid administration.     

Effect of blood conservation in open-heart surgery: a comparison of 3 different methods

Conventional blood conservation techniques have been insufficient to decrease blood transfusion requirement in open-heart surgery. Blood conservation and erythropoietin administration were performed to avoid homologous blood transfusion. Intraoperative autotransfusion has been routinely used in cardiac operations with cardiopulmonary bypass in our hospital. To evaluate the effect of conservation techniques, 286 patients were divided into four groups. In group I (23 patients), autologous whole blood was drawn and saved one to two weeks before operation. In group II (50 patients), erythropoietin preparation was given subcutaneously once a week and autologous blood conservation was also performed in the same manner as group I. In group III (48 patients), intra-operative hemodilutional autologous blood transfusion was performed. In group IV, as a control group (165 patients), only intra-operative autotransfusion was used. Homologous blood transfusion was avoided in 83% of group I patients, in 90% of group II, in 82% of group III, and 29% of group IV. In addition, in group II the hemoglobin value at the time of discharge was significantly higher than those of other groups (p < 0.05-0.01). Thus, conventional blood conservation techniques plus subcutaneous administration of erythropoietin was very effective to increase the rate of "non-blood" open-heart surgery.     

A single dose of morphine sulfate increases the incidence of vomiting after outpatient inguinal surgery in children

BACKGROUND: In children, opioids are valuable both for their analgesic properties and for their salutary effect on emergence delirium. Although intraoperative administration of opioids is often cited as the cause of postoperative emesis, few data quantitating the magnitude of this effect exist. METHODS: Patients undergoing inguinal surgery as outpatients were randomly assigned to one of two groups. One group received a single intravenous dose of morphine 0.1 mg/kg (morphine group), and the other (control) group had the identical anesthetic but instead received saline. Intravenous ketorolac was administered in response to verbal complaints of pain or a Children's Hospital of Eastern Ontario Pain Score greater than 9 on two successive evaluations performed at 5-min intervals. The authors compared the incidence of postoperative emesis and emergence, behavior, and pain scores between the two groups. RESULTS: Patients in the morphine group (n = 48) were 5.6 +/- 2.8 yr old and weighed 20.8 +/- 7.8 kg, and those in the control group (n = 49) were 4.5 +/- 2.9 yr old and weighed 18.9 +/- 9.2 kg. More patients in the morphine group were cooperative and deeply asleep both on arrival and through the first 30 min of their stay in the postanesthesia care unit (PACU) (P < 0.05). Sixty-three percent of the children in the control group received ketorolac in the PACU compared with 20% of the morphine group (P < 0.01). The incidence of emesis for the 24 h after arrival in the PACU was 56% for those who received morphine compared with 25% in the control group (P < 0.01). CONCLUSIONS: For children undergoing inguinal surgery, the administration of a single dose of intravenous morphine after the induction of anesthesia smooths emergence from anesthesia as assessed by improved cooperation and sedation in the PACU, decreases the need for postoperative analgesics, but increases the incidence of vomiting in the first 24 h after surgery.     

Identification of X-ray-induced complex chromosome exchanges using fluorescence in situ hybridization: a comparison at two doses

Complex chromosome exchanges are defined as interactions between three or more breaks, in two or more chromosomes. In this study, a sequential hybridisation technique was developed to visualize a given chromosome pair: green (chromosomes 1, 5 and 7), all centromeres red and the remaining chromosomes blue. Primary human fibroblasts were irradiated in G1 with 4 and 6 Gy 250-kV X-rays. After 4 Gy, a total of 387 simple aberrations (defined as translocations or dicentrics with fragments) and 116 complex aberrations were identified. After 6 Gy these aberrations numbered 225 and 110 respectively. Using a break-rejoin scheme, which describes interactions between breaks within a complex as independent events we modelled the complex 'mix' present after 4 Gy. At 6 Gy the same model could be used for chromosomes 5 and 7, but chromosome 1 frequencies could only be explained if we biased the interactions, such that two-breaks-in-one-chromosome events occur predominantly in chromosome 1. From these predicted interactions we also calculated the number of apparently simple exchanges that are actually complex derived. These accounted for 20% of those observed after 4 Gy and 33% after 6 Gy. Therefore, with this FISH assay, an estimated 35 and 54% of all exchanges are derived from complexes after 4 and 6 Gy respectively.     

Pain control after dental surgery: a double-blind, randomised trial of lornoxicam versus morphine

Lornoxicam is a new non-steroidal anti-inflammatory drug of the oxicam class. This randomised, double-blind, placebo controlled trial compared the analgesic efficacy and tolerability of intramuscular (IM) injections of lornoxicam (4, 8, 16 and 20 mg) with morphine (10 and 20 mg) and placebo in 252 patients with mainly moderate to severe pain following surgical removal of an impacted mandibular third molar. Patients treated with lornoxicam or morphine experienced a significantly greater cumulative pain relief over the 4-h post-injection period (TOTPAR0-4) than placebo recipients. This effect appeared to be dose-dependent, with patients in the lornoxicam 4 mg or morphine 10 mg groups recording significantly lower TOTPAR0-4 scores than patients in the higher dosage groups of these drugs. No significant difference was detected between the morphine 20 mg group and the lornoxicam 8, 16 and 20 mg groups. Lornoxicam was well tolerated at all doses and was associated with a significantly lower incidence of adverse events than morphine 10 or 20 mg. Thus, the analgesic efficacy of IM lornoxicam at doses > or = 4 mg is superior to placebo, and doses > or = 8 mg are at least as effective as IM morphine 20 mg. Furthermore, lornoxicam possesses a more favourable tolerability profile than morphine and thus represents an attractive alternative for the treatment of moderate to severe acute pain.     

Randomized trial comparing two different high doses of methylprednisolone in MS: a clinical and MRI study

OBJECTIVE: To assess the efficacy of two different high doses of intravenous methylprednisolone (IVMP) for the treatment of relapses in MS. BACKGROUND: IVMP is the treatment of choice for MS relapses, but it is unknown whether its effects are dose related. METHODS: We conducted a double-blind, randomized study. Follow-up included serial clinical and MRI recordings at baseline and at 7, 15, 30, and 60 days after the beginning of treatment. Outcome measures were the number of brain and cervical spinal cord MRI contrast-enhancing lesions, and the Expanded Disability Status Scale score. RESULTS: Both treatment regimens improved clinical scores and reduced the number of MRI enhancing lesions during the follow-up period. The higher dose of IVMP was significantly more effective than the lower dose in reducing the number of MRI contrast-enhanced lesions at 30 and 60 days, mainly by decreasing the rate of new lesion formation. CONCLUSIONS: The higher dosage of IVMP has a more powerful and prolonged action in maintaining blood-brain barrier integrity after a clinical relapse.     

Randomized comparison of tamoxifen and two separate doses of toremifene in postmenopausal patients with metastatic breast cancer

PURPOSE: To perform a randomized three-arm comparison of tamoxifen (TAM; 20 mg/d) and two separate doses of toremifene (TOR; 60 mg/d [TOR60] and 200 mg/d [TOR200]) in postmenopausal patients with hormone receptor-positive or -unknown metastatic breast cancer. MATERIALS AND METHODS: Six hundred forty-eight patients with hormone receptor-positive or -unknown metastatic breast cancer were randomly assigned to receive TAM (n = 215), TOR60 (n = 221), or TOR200 (n = 212). RESULTS: The combined response rates (by intent to treat) were as follows;: TAM, 44%; TOR60, 50%; and TOR200, 48%. Complete and partial response rates were as follows: TAM, 19%; TOR60, 21%, and TOR200, 23% (not statistically different). Median times to progression and overall survival were not significantly different. Adverse events (lethal, serious but nonlethal, and important but non-life-threatening) were similar in all three arms, except that patients in the TOR200 arm had a statistically significantly increased rate of nausea (37% v 26% and 26% for TOR200, TAM, and TOR60, respectively; P = .027). Quality-of-life assessments were not different among the three arms. CONCLUSION: The activity, toxicity, and side effects of TOR in postmenopausal women with hormone receptor-positive or -unknown metastatic breast cancer are similar if not equivalent to those of TAM. We detected no clear evidence of a dose-response effect for TOR. TOR60 is an effective and safe agent for the treatment of postmenopausal women with hormone receptor-positive metastatic breast cancer and can be considered an alternative to TAM as first-line treatment for such patients.     

Interleukin-6 and a delay of neutrophil apoptosis after major surgery

Surgical treatments affect host immune systems. Apoptosis of the circulatory lymphocytes and an elevation of the number of neutrophils are induced by surgery. These alterations are not dependent only on the stress hormone. The course of neutrophilia and the serum concentration of interleukin-6 are given after various surgical treatments. Neutrophil-mediated lung injury is discussed.     

No short-term changes of cognitive performance and mood after single doses of two different lithium retard preparations

This double-blind crossover study investigated the effects of single doses of lithium carbonate (36.6 mval), lithium-sulfate (36 mval), and placebo within the first six hours after administration. The subjects were nine healthy volunteers. The target variables were physical complaints, mood, memory, visuomotor speed, and time estimation. Subjects showed no significant impairment of performance in the cognitive tests and no subjective changes of well-being under lithium. Therefore, it seems that lithium-induced alterations of memory and mood reported in the literature develop very slowly and do not appear after a single dose.