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.     

Postoperative hypoxaemia: continuous extradural infusion of bupivacaine and morphine vs patient-controlled analgesia with intravenous morphine

We carried out a randomized prospective study in 60 patients who had undergone major abdominal surgery for cancer. For postoperative pain control, 30 patients received continuous extradural infusion of 0.125% bupivacaine 12.5 mg h-1 and morphine 0.25 mg h-1 (EXI group) and 30 received patient-controlled analgesia (PCA) with intravenous morphine (1 mg bolus, 5-min lock-out and maximum dose 20 mg 4h-1). Both groups had general anaesthesia. The two groups were compared for postoperative pain scores, satisfaction, sedation and oxygen saturation. Oxygen saturation was recorded continuously the night before surgery and for two consecutive postoperative nights. Episodes of moderate desaturation (90% > SpO2 85%) were more frequent in the EXI group than in the PCA group (P < 0.05). Pain scores were lower in the EXI group compared with the PCA group at rest and while coughing (P < 0.05). No significant difference was found for patient sedation and satisfaction.     

Pharmacokinetics of morphine and its glucuronides after intravenous infusion of morphine and morphine-6-glucuronide in healthy volunteers

Steady-state pharmacokinetics of morphine and morphine-6-glucuronide (M-6-G) after intravenous administration of either morphine or M-6-G were determined in healthy volunteers. With a dosing regimen calculated on the basis of data obtained in a first series of experiments in four subjects (morphine: intravenous loading dose of 0.24 mg/kg for 5 minutes and an intravenous infusion of 0.069 mg.kg-1.hr-1 for 4 hours; M-6-G: loading dose of 0.011 mg/kg for 5 minutes and an infusion of 0.006 mg.kg-1.hr-1 for 4 hours), it was possible to yield plasma concentrations of morphine and M-6-G in another four subjects close to predefined targeted levels (35 and 45.5 ng/ml morphine and M-6-G, respectively). This dosing regimen may be used in further pharmacodynamic studies to compare the analgesic effects of morphine and M-6-G. In addition, metabolite kinetics of M-6-G were calculated as a function of time with use of a linear systems approach to the estimation of rate and fraction of morphine glucuronidation to M-6-G.     

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.     

Intraoperative intravenous ketamine in combination with epidural analgesia: postoperative analgesia after renal surgery

We designed this double-blinded, randomized, controlled study to evaluate the effect of small-dose ketamine IV in combination with epidural morphine and bupivacaine on postoperative pain after renal surgery. An epidural catheter was inserted, and the administration of morphine and bupivacaine was started before surgery. Forty patients were assigned to one of two groups (ketamine or control). The ketamine group was administered a ketamine bolus and infusion during surgery. The median visual analog pain scale (VAS) scores at rest were significantly lower in the ketamine group during the first 6 h (P < 0.01). VAS pain scores on coughing were also significantly lower in the ketamine group (P < 0.01). Cumulative postoperative total analgesic consumption was less in the ketamine group on Days 1 and 2 (P < 0.001). The first analgesic demand time was shorter in the control group (9.2 +/- 11.5 min) than in the ketamine group (22.3 +/- 17.1 min) (P < 0.0001). The incidence of nausea and pruritus was more frequent in the control group (P < 0.05). In conclusion, postoperative analgesia was more effective when spinal cord and brain sensitization were blocked by a combination of epidural morphine/bupivacaine and IV ketamine. IMPLICATIONS: Renal nociception conducted multisegmentally by both the spinal nerves (T10 to L1) and the vagus nerve cannot be blocked by epidural analgesia alone. We demonstrated that IV ketamine had an improved analgesic or opioid-sparing effect when it was combined with epidural bupivacaine and morphine after renal surgery.     

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].     

Diazepam: intravenous infusion in the treatment of status epilepticus

A case of Pierre Robin-Syndrome with associated rib gap defects is reported. Rib defects are described still now only in childs with micrognathia. Respiratory embrassement may be caused.     

Coronary vasomotion during dynamic exercise: influence of intravenous and intracoronary nicardipine

OBJECTIVES: Our aim was to evaluate the influence of a calcium channel blocking agent of the dihydropyridine group (nicardipine) on coronary vasomotion during dynamic exercise. BACKGROUND: Coronary vasomotion plays an important role in the pathophysiology of myocardial ischemia. METHODS: Twenty-nine patients with coronary artery disease were studied at rest and during bicycle exercise with the use of biplane quantitative coronary angiography. Twelve patients without pretreatment (group 1) served as control subjects. Seventeen patients (group 2) received nicardipine, either 0.2 mg by intracoronary injection (n = 9) or 2.5 mg intravenously (n = 8) before exercise. RESULTS: In the control group there was exercise-induced vasoconstriction (-29%, p < 0.001) of the stenotic segment but coronary vasodilation (+22%, p < 0.05) of the normal vessel segment. In group 2, nicardipine induced coronary vasodilation of both the normal (+16%, p < 0.001) and the stenotic vessel segment (+35%). During subsequent exercise there was some additional vasodilation of normal (+4%, p = NS) and stenotic arteries (+5%, p = NS). There was no difference between either intracoronary or intravenous nicardipine with regard to vasodilation. Application of sublingual nitroglycerin was associated with significant vasodilation of the normal vessel segment in groups 1 (+18%, p < 0.05) and 2 (+15%, p < 0.001). The stenotic vessels showed a significant increase in percent cross-sectional area after nitroglycerin in groups 1 (+12%, p = NS) and 2 (+51%, p < 0.001). Exertional angina pectoris occurred less frequently in group 2 (18%) than in group 1 (67% [p < 0.005 vs. group 2]); group 2 also had a smaller increase in mean pulmonary artery pressure (+14 vs. +21 mm Hg, p < 0.05). CONCLUSIONS: Exercise induces vasoconstriction of stenotic, but vasodilation of normal, coronary vessel segments. Intravenous and intracoronary nicardipine prevent vasoconstriction of stenotic coronary arteries during exercise and exert a significant anti-ischemic effect. The combination of two anti-ischemic drugs, nitroglycerin and nicardipine, has an additive effect on coronary vasomotion that is seen only in the stenotic vessel segment. Thus, the anti-ischemic action of nicardipine is mainly due to a primary effect on coronary vasomotor response rather than to secondary effects such as changes in loading conditions.     

Comparison of morphine and morphine with ketamine for postoperative analgesia

In addition to the patient's history and a thorough clinical investigation, magnetic resonance imaging (MRI) of the temporomandibular joint (TMJ) has been introduced to complete the findings for the diagnosis of internal derangement of the TMJ. However, 'dynamic information' is desirable to help us to understand the mechanism of internal derangement. This information is given for example by electronic axiography recording systems. The lack of any ability to assess joint function dynamically in MRI is a point of criticism. Using a computer-driven pseudodynamic MRI system (CINE mode) 'dynamic information' should be now available. In this investigation 21 patients with TMJ disorders were examined using both conventional static MRI and CINE mode. For the diagnosis of an anterior displaced disc with or without reduction in 18 cases (86%) it was only necessary to consider two static MRIs: a closed mouth position and a maximal open mouth position. Comparison showed there was no advantage in using CINE mode. Contrast and resolution of the static MRIs were shown to be better and so additional findings such as joint effusion and disc deformation could be diagnosed on static MRIs with greater certainty. Only in three (14%) cases was the dynamic information from CINE mode useful for the diagnosis of the displacement of the disc.     

Variability of morphine disposition during long-term subcutaneous infusion in terminally ill cancer patients

OBJECTIVE: To study the plasma concentrations of morphine and its glucuronides to assess the intra- and interindividual variability of the disposition of morphine administered by subcutaneous infusion in cancer patients. METHODS: Blood samples were taken repeatedly in eight patients with severe cancer pain who were being treated with morphine (60-3000 mg per day) via chronic (8-160 days) subcutaneous infusion. Venous blood samples were collected at least weekly and, when possible, on 3 consecutive days after dose adaptation or any other major change in the patients' treatment. Concentrations of morphine and its glucuronides in plasma were measured after solid-phase extraction using a validated high-performance liquid chromatography assay. The stability of the morphine solutions was determined by repeated measurement of the concentrations of morphine and its degradation products in the solutions. RESULTS: The morphine concentration in the infusion solutions remained unchanged during storage and infusion. The plasma concentrations of morphine and its glucuronides were within the ranges reported in the literature. There was, as expected, a large interindividual variability: from patient to patient, the mean of the normalised plasma concentrations ranged from 0.3 ng.ml(-1).mg(-1) to 0.8 ng.ml(-1).mg(-1) for morphine, from 1.0 ng.ml(-1).mg(-1) to 3.1 ng.ml(-1).mg(-1) for morphine-6-glucuronide and from 6.8 ng.ml(-1).mg(-1) to 24.3 ng.ml(-1).mg(-1) for morphine-3-glucuronide. Intraindividual variability was also important. The residual standard deviation of the mean normalised plasma concentrations calculated for each patient ranged from 26% to 56% for morphine, from 20% to 51% for morphine-6-glucuronide and from 20% to 49% for morphine-3-glucuronide. The normalised plasma concentrations of morphine and its glucuronides did not increase with dose or time, and no explanation for the pronounced pharmacokinetic intraindividual variability was found. CONCLUSION: During subcutaneous infusion of morphine, there is a large intra- and interindividual variability of the morphine disposition which could be of clinical relevance.     

Misperfusion of the liver during hepatic artery infusion chemotherapy: value of preoperative angiography and postoperative pump scintigraphy

OBJECTIVE: One purpose of this study was to determine if patients who have anatomic variations in their hepatic arteries are at increased risk for complications associated with the use of intrahepatic arterial infusion pumps. We also tried to determine the value of perfusion studies obtained with 99mTc-microspheres or 99mTc-macroaggregated albumin in detecting postoperative hepatic or visceral misperfusion and in predicting complications in patients with anatomic variants despite pre- or intraoperative attempts to correct the arterial abnormality. SUBJECTS AND METHODS: We prospectively compared findings on scintigrams obtained after delivering the radionuclide through intrahepatic arterial infusion pumps with anatomic variations in hepatic arteries seen on celiac and superior mesenteric hepatic arteriograms obtained before placement of the pump in 49 consecutive patients with colon carcinoma metastatic to the liver. RESULTS: Despite pre- or intraoperative attempts to correct arterial abnormalities to ensure optimal perfusion of the liver in 24 patients with hepatic arterial anomalies seen on preoperative arteriograms, only two patients had normal findings on postoperative perfusion studies performed with 99mTc-microspheres and/or 99mTc-macroaggregated albumin. Abnormalities included perfusion of extrahepatic organs, including the spleen in 12 patients, stomach in seven, bowel in four, and pancreas in three. Eight patients had no perfusion of the left lobe of the liver, and three had no perfusion of the right lobe. Two patients had minimal or no perfusion of both lobes. In 23 of 25 patients with no demonstrable variations in vascular anatomy on preoperative celiac and superior mesenteric arteriograms, findings on hepatic pump scintigrams were normal. Of the 24 patients with abnormal scintigraphic findings, 20 had subsequent clinical complications. However, only two of the 25 patients with normal scintigraphic findings had clinical complications. CONCLUSION: Our results indicate that patients with anatomic variations in the hepatic arterial system are at high risk for misperfusion during chemotherapy despite pre- or intraoperative efforts to alter the perfusion for chemotherapeutic agents delivered by intrahepatic arterial infusion pumps. Misperfusion can be detected by using pump scintigraphy, and therefore patients should be closely monitored with 99mTc-macroaggregated albumin perfusion studies to ensure successful delivery of the chemotherapeutic agents and to avoid serious clinical complications caused by inadvertent perfusion of other organs.     

Morbidity during the first year of life in small for gestational age infants

OBJECTIVE: To study the effect of early postnatal dexamethasone (days 1-3) on the incidence and severity of chronic lung disease in preterm infants with respiratory distress syndrome. METHODS: A multicentre, randomised, placebo controlled, blinded study was carried out in 18 neonatal intensive care units in Israel. The primary outcome measure was survival to discharge without requirement for supplemental oxygen therapy beyond 28 days of life. The secondary outcome measures were requirement for mechanical ventilation at 3 and 7 days, duration of ventilation or oxygen therapy, need for subsequent steroids for established chronic lung disease and incidence of major morbidities. RESULTS: The study consisted of 248 infants (dexamethasone n = 132; placebo n = 116). No differences were found in the outcome variables except for a reduction in requirement for mechanical ventilation at age 3 days in treated infants (dexamethasone 44%, placebo 67%; P = 0.001). Gastrointestinal haemorrhage, hypertension, and hyperglycaemia were more common in treated infants, but no life threatening complications, such as gastrointestinal perforation, were encountered. CONCLUSIONS: These data do no support the routine use of early postnatal steroids, but may justify further study in a selected, high risk group of infants.     

Intermittent administration of furosemide versus continuous infusion in the postoperative management of children following open heart surgery

OBJECTIVE: To compare the amount of furosemide needed to fulfil defined criteria for renal output if given intermittently or as a continuous infusion and to compare the effect of these two regimens on hemodynamic variables and urine electrolyte concentrations. DESIGN: Prospective randomized study of postoperative hemodynamically stable pediatric cardiac patients. The patients were given furosemide according to the urine output, either as an intermittent bolus injection or as a continuous infusion. SETTING: Pediatric intensive care unit in a university hospital. PATIENTS: The patients were randomly assigned before admission to either the intermittent i.v. or the continuous furosemide i.v. infusion group. MEASUREMENTS AND RESULTS: Demographic and hemodynamic data were recorded for a maximum of 72 h, as were furosemide dose, urine output, and fluid and inotropic drug requirements. Forty-six patients completed the study. Maximal hourly urine output was significantly higher in the intermittent group. A significantly lower dose of furosemide in the intermittent group produced the same 24-h urine volume as in the continuous infusion group. CONCLUSIONS: Intermittent furosemide administration may be recommended in hemodynamically stable postoperative pediatric cardiac patients because of less drug requirement. However, the high maximal urine output may cause hemodynamic problems in patients who depend on high inotropic support.     

Comparison of propacetamol and morphine in postoperative analgesia]

To compare the analgesic efficacy and tolerance of propacetamol and morphine, 80 patients in good clinical condition were included in a prospective, parallel, randomized double blind trial after elective surgery expected to elicit light to moderate postoperative pain. At the end of general anesthesia, 40 patients received 30 mg/kg propacetamol and 40 0.2 mg/kg morphine, as a 15-min intravenous infusion. The groups were similar for age, weight and duration of anesthesia. Supplemental analgesia had to be given in 7 cases from the propacetamol group vs. 2 cases from the morphine group. The postoperative pain, evaluated 7 times during 4 h from the end of infusion with a visual analog scale, revealed a modest advantage for morphine at 0.5 and 4 h (p = 0.05). The respiratory rate was slightly lower after morphine (p = 0.02). No significant differences were observed in blood oxygen saturation, blood pressure, heart rate, body temperature and vigilance evaluated by the trailmaking test. Nausea was present in 4 cases under propacetamol and 3 under morphine, and pruritus in 2 and 7 cases, respectively. In conclusion, propacetamol may represent an alternative to morphine for pain prevention after mildly to moderately painful surgery in situations where the use of opioids is unsuitable.     

Creatine supplementation and age influence muscle metabolism during exercise

Young [n = 5, 30 +/- 5 (SD) yr] and middle-aged (n = 4, 58 +/- 4 yr) men and women performed single-leg knee-extension exercise inside a whole body magnetic resonance system. Two trials were performed 7 days apart and consisted of two 2-min bouts and a third bout continued to exhaustion, all separated by 3 min of recovery. 31P spectra were used to determine pH and relative concentrations of Pi, phosphocreatine (PCr), and beta-ATP every 10 s. The subjects consumed 0.3 g . kg-1 . day-1 of a placebo (trial 1) or creatine (trial 2) for 5 days before each trial. During the placebo trial, the middle-aged group had a lower resting PCr compared with the young group (35.0 +/- 5.2 vs. 39.5 +/- 5.1 mmol/kg, P < 0.05) and a lower mean initial PCr resynthesis rate (18.1 +/- 3.5 vs. 23.2 +/- 6.0 mmol . kg-1 . min-1, P < 0.05). After creatine supplementation, resting PCr increased 15% (P < 0.05) in the young group and 30% (P < 0.05) in the middle-aged group to 45.7 +/- 7.5 vs. 45.7 +/- 5.5 mmol/kg, respectively. Mean initial PCr resynthesis rate also increased in the middle-aged group (P < 0.05) to a level not different from the young group (24.3 +/- 3.8 vs. 24.2 +/- 3.2 mmol . kg-1 . min-1). Time to exhaustion was increased in both groups combined after creatine supplementation (118 +/- 34 vs. 154 +/- 70 s, P < 0.05). In conclusion, creatine supplementation has a greater effect on PCr availability and resynthesis rate in middle-aged compared with younger persons.     

Myocardial tomography with technetium-99m-tetrofosmin during intravenous infusion of adenosine triphosphate

The purpose of this study was to determine the biodistribution of 99mTc-tetrofosmin during intravenous infusion of adenosine triphosphate (ATP) and to evaluate the potential diagnostic value of myocardial tomography with 99mTc-tetrofosmin during ATP infusion for the detection of coronary artery disease. METHODS: Myocardial 99mTc-tetrofosmin imaging with ATP infusion and coronary arteriography were performed on 65 patients with suspected coronary artery disease. ATP was infused intravenously at a rate of 0.16 mg/kg/min for 5 min, and 370 MBq of 99mTc-tetrofosmin was injected 3 min after the start of ATP infusion. Myocardial SPECT imags were obtained 60 min later. Then, 740 MBq of 99mTc-tetrofosmin was administered at rest, and myocardial SPECT was repeated. Regional uptakes of 99mTc-tetrofosmin were scored from 4, normal, to 0, no activity. Serial 5-min planar images were obtained in the anterior projection at 15, 30, 45 and 60 min after the 99mTc-tetrofosmin injection in 10 patients. Heart-to-lung and heart-to-liver count ratios were defined from the serial planar images. RESULTS: Adverse effects of ATP infusion were mild and transient. A heart-to-lung ratio after ATP infusion was high even at 15 min (3.40 +/- 0.33) and gradually increased with time. A heart-to-liver ratio after ATP was 0.53 +/- 0.40 at 15 min and increased with time. A heart-to-liver ratio reached 0.99 +/- 0.25 (p < 0.01) after 45 min and 1.32 +/- 0.36 (p < 0.01) after 60 min. The sensitivity and specificity for detecting coronary artery disease by myocardial SPECT with ATP were 89% (39/44) and 86% (18/21), respectively. CONCLUSION: This study shows the favorable biodistribution of 99mTc-tetrofosmin after intravenous infusion of ATP. A one-day imaging protocol of 99mTc-tetrofosmin tomography with ATP is feasible and has high diagnostic accuracy for coronary artery disease.     

Cardiac rhythm abnormalities during intravenous immunoglobulin G infusion for treatment of thrombocytopenia

Thrombolysis of arterial occlusions has limitations, e.g. it requires extensive time for thrombolysis, occlusions may be resistant to lysis, and the rate of reocclusions may be high. c7E3 Fab inhibits platelet aggregation by binding to the GPIIb/IIIa receptor on platelets. Experimentally, this monoclonal antibody has been shown to decrease, the time required for lysis, and to prevent reocclusion. This is the first report on the adjunctive use of c7E3 Fab in peripheral arterial occlusions in humans. Three patients with occlusion of the iliac or femoropopliteal artery were treated with c7E3 Fab (bolus injection of 0.25 mg/kg KG + i.v.-application 12 micrograms/min for 12 h). In addition, the patients received urokinase (100,000 IU bolus + 100,000 IU/h). Heparin (5,000 IU bolus + 1,000 IU/h) and acetylsalicylate (100 mg/day/p.o.). Occlusion length ranged between 6-40 cm. Therapy was successful in all patients. During the follow-up period (4-6 months) no reocclusion occurred. There were no serious side effects like major bleeding or thrombocytopenia. We conclude that the applied doses appear safe. Even the time required for thrombolysis was short, a conclusion in respect of a significant reduction of the time required for lysis can be drawn only after further controlled studies.     

The influence of biliary infection on the postoperative course after biliary tract surgery

A prospective clinicobacteriological study was undertaken in 167 patients undergoing biliary surgery so as to assess the possible influence of the endogenous preoperative biliary infection on postoperative morbidity. Bile cultures were positive in 33% (55 patients); in those undergoing cholecystectomy alone this finding was present in 23% while in those in whom a choledochotomy was also performed cultures were positive in 65%. The incidence of wound infection was found to be twice as high in those undergoin choledochotomy as in those undergoing cholecystectomy alone--37.8% vs. 18.5%. There was no appreciable difference in the rate of wound infection when a routine appendectomy was performed during biliary tract surgery. Among the 38 patients with wound infection, bile cultures were positive in 16. In 13 cases the offending organism in the wound was identical with that recovered from the bile coulture. This finding suggests an endogenous source for the wound infection. This study further indicated that wound infection is most likely to be encountered in patients with pathogenic organisms in the bile, in the aged and in those whose resistance to infection has been lowered by concomitant disease.     

Plasma amino acid patterns during supplemental intravenous nutrition of low-birth-weight infants

In 42 low-birth-weight infants (smaller than 1,200 gm), we have compared the effects of intravenous nutrition supplement versus conventional feedings on growth, morbidity, mortality, and plasma amino acid patterns. Despite similar total caloric intake in INS and control groups, weight gain was greater in the INS infants. The overall mortality rate did not differ in the two groups. Nonsurviving infants receiving INS lived longer (mean equal to 30 days) than nonsurviving CON infants (mean equal to 5 days). Complications were equally frequent in both groups except that hyperglycemia occurred more often in infants receiving INS. The plasma aminogram of the LBW infant is described and compared to those of the full-term infant and adult. Hypoaminoacidemia was present at birth in the LBW infants, concentrations of glutamine, alamine, glycine, histidine, and ornithine being significantly (P smaller than 0.05) below FT values. During INS, elevations of threonine, serine, and methionine above FT values occurred. Glutamine remained subnormal despite INS. Recommendations for an INS solution more suitable for use in LBW infants are presented.