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Background Dexmedetomidine (DEX) is a highly selective α-2 agonist with many desirable effects including analgesia, improvement of hemodynamic stability, and potential myocardial and renal protection. The aim of this study was to investigate the effect of DEX on patients undergoing off-pump coronary artery bypass (OPCAB) grafting with regard to less pain medication, earlier extubation, faster transfer to normal ward, and cardiac protection. Patients and Methods From January 2012 to March 2015, 464 patients receiving OPCAB were included for retrospective analysis. After propensity matching (1:1), two groups (DEX vs. propofol, n = 129) could be compared. Continuous and categorical variables were reported as mean ± standard deviation or percentages, and compared with the chi-square test and the Mann–Whitney's test, respectively. Results In the DEX group, less use of pain medication in the initial phase at intensive care unit was observed. During the first 2 hours, DEX patients received more nicomorphine (DEX 8 ± 3.2 mg vs. propofol 6 ± 4 mg, p Conclusion Early postoperative DEX application supports the fast-track strategy in patients after OPCAB through enabling rapid extubation, effective pain control, and reduced occurrence of new-onset AF. We are confident to give precedence to DEX over propofol as the new routine medication during postoperative patient transfer.

We have compared the efficacy of patient-controlled interscalene analgesia (PCIA) using ropivacaine with patient-controlled analgesia (PCA) using nicomorphine in 60 patients (n = 30 in each group), in a prospective, randomized study. In both groups, all patients received interscalene block with 0.75% ropivacaine before induction of anaesthesia. Six hours after interscalene block, patients in group PCIA received continuous infusion of 0.2% ropivacaine at a rate of 5 ml h-1 with a bolus dose of 3 or 4 ml and a lockout time of 20 min; patients in group PCA received continuous infusion of nicomorphine 0.5 mg h-1 and a bolus dose of 2 or 3 mg with a lockout time of 20 min. Control of pain was significantly better from 12 to 48 h after operation (except at 42 h) in group PCIA. Nausea and pruritus occurred significantly more frequently in group PCA. Patient satisfaction was greater in group PCIA. We conclude that the use of 0.2% ropivacaine using PCIA was an efficient way of managing pain after major shoulder surgery and compared favourably with PCA nicomorphine in terms of pain relief, side effects and patient satisfaction.

After epidural administration of 15 mg 3, 6-dinicotinoylmorphine (nicomorphine) in 10 patients undergoing pulmonary surgery, the parent compound was quickly metabolized into the metabolites 6-mononicotinoylmorphine and morphine. The mean apparent half-lives (+/- SD) of elimination were 10 min (0.165 h +/- 0.053 h) for 3,6-dinicotinoylmorphine and 1.77 h +/- 1.23 h for 6-mononicotinoylmorphine. Morphine is subsequently metabolized into morphine-3-glucuronide and morphine-6-glucuronide. The apparent half-lives of morphine, morphine-3-glucuronide, and morphine-6-glucuronide are similar: 3.63 h +/- 1.63 h, 4.10 h +/- 0.57 h, and 4.20 h +/- 1.64 h respectively. The possible glucuronide conjugate of 6-mononicotinoylmorphine was not detected. The prodrug 3,6-dinicotinoylmorphine was biotransformed into three active compounds: 6-mononicotinoylmorphine, morphine, and morphine-6-glucuronide.

After i.m. injection nicomorphine is relatively slowly absorbed from the muscular depot and is found in the serum for approximately 1 h. The rate of absorption differs between patients and governs the overall pharmacokinetic profile of the compound. The relative AUCs were nicomorphine 18%, 6-nicotinoylmorphine 17%, and morphine 65%. Nicomorphine and 6-nicotinoylmorphine have significantly higher AUCs after i.m. injection than after i.v. injection, while the AUC of morphine and the total AUC show no difference between the two modes of administration.

In ten patients who received an epidural injection of 15 mg of nicomorphine, the compound was relatively slowly released from the epidural space and was found in plasma for approximately 1.5 h. Nicomorphine is relatively slowly metabolized into 6-nicotinoylmorphine and morphine. The rate of release is patient-dependent. The relative AUC values are 15.3% for nicomorphine, 23.9% for 6-nicotinoylmorphine and 60.8% for morphine. The mean clinical effect lasts for 18.2 +/- 10.1 h.

Objectives. To study the effect of morphine and opiates on fracture risk. Design. Case-control study. Setting. Nationwide register-based study. Subjects. Cases were all subjects with any fracture sustained during the year 2000 (n = 124 655). For each case, three controls (n = 373 962) matched on age and gender were randomly drawn from the background population. The primary exposure variables were use of morphine and opiates. Morphine and other opiates had been used by 10 015 (8.0%) of the case subjects and 12 108 (3.2%) of the controls. Adjustments were made for several confounders including prior fracture, and use of weak analgesics [nonsteroidal anti-inflammatory drugs, acetylsalicylic acid (ASA) and acetaminophene]. The effect of dose was examined by stratifying for cumulated dose (defined daily dose). Main outcome measure. Fracture. Results. Morphine (1.47, 95% CI 1.37-1.58), fentanyl (2.23, 95% CI 1.89-2.64), methadone (1.39, 95% CI 1.05-1.83), oxycodone (1.36, 95% CI 1.08-1.69), nicomorphine (1.57, 95% CI 1.38-1.78), ketobemidone (1.07, 95% CI 1.02-1.13), tramadol (1.54, 95% CI 1.49-1.58) and codeine (1.16, 95% CI 1.12-1.20) were all associated with an increase in overall fracture risk. No increase was present for buprenorphine (0.86, 95% CI 0.79-0.95), pethidine (0.98, 95% CI 0.89-1.08), dextropropoxiphene (1.02, 95% CI 0.90-1.16), and combinations of ASA and codeine (0.94, 95% CI 0.88-1.01). Conclusions. An increased fracture risk is seen in users of morphine and opiates. The reason for this may be related to the risk of falls due to central nervous system effects such as dizziness. Language: en

To compare the effect of combined intrathecal morphine and sufentanil with low-dose iv sufentanil during propofol anesthesia for fast-track cardiac surgery.Twenty-four consecutive patients with normal cardiopulmonary function who were scheduled for elective cardiac surgery were randomized to receive either a continuous iv infusion of sufentanil 0.9 to 1.8 microg x kg(-1) x min(-1) (13 patients), or a single lumbar intrathecal dose of sufentanil 50 micro g and morphine 500 micro g (11 patients). We prospectively studied perioperative analgesia, time to extubation and early postoperative maximal inspiratory capacity in the two groups. In the intensive care unit, the medical and nursing staff were blinded to the analgesic technique.Intrathecal sufentanil morphine allowed a shorter duration of intubation (104 +/- 56.5 min vs 213 +/- 104 min; P = 0.01), reduced the need for postoperative analgesia with nicomorphine (equipotent to morphine) (0.7 +/- 0.4 mg x hr(-1) vs 1.2 +/- 0.4 mg x hr(-1); P = 0.008) and improved postoperative maximal inspiratory capacity (53.4 +/- 16.1 vs 38.4 +/- 12.5% of the norm; P = 0.05).In low-risk patients undergoing coronary artery bypass graft or valve surgery, combined intrathecal sufentanil and morphine with a target-controlled infusion of propofol satisfies the goals of fast-track cardiac surgery.

The pharmacokinetics of 30 mg nicomorphine after rectal administration with a suppository are described in 8 patients under combined general and epidural anaesthesia. No nicomorphine or 6-mononicotinoylmorphine could be detected in the serum. Morphine appeared almost instantaneously with a lag-time of 8 min and had a final elimination half-life of 1.48 +/- 0.48 h. Morphine was metabolized to morphine-3-glucuronide and morphine-6-glucuronide. These glucuronide conjugates appeared after a lag-time of 12 min and the half-life of these two glucuronide conjugates was similar: about 2.8 h (P0.8). The glucuronide conjugate of 6-mononicotinoylmorphine was not detected. In the urine only morphine and its glucuronides were found. The renal clearance value for morphine was 162 ml.min-1 and for the glucuronides 81 ml.min-1. This study shows that administration of a suppository with 30 mg nicomorphine gives an excellent absolute bioavailability of morphine and its metabolites of 88%. The lipid-soluble prodrug nicomorphine is quickly absorbed and immediately hydrolysed to morphine.

Epidural injections of 5 mg nicomorphine in 20 ml 5% glucose wee given to 10 gynaecological patients to provide intra-operative and post-operative analgesia. Signs of changed nociception appeared within 5 min. The maximum change occurred within 20 min. Effectiveness was at least 3 1/2 h. After an observation period of 30 min, light general anaesthesia is supplemented to give excellent operating conditions. It is suggested that opiates produce these effects by a direct action on the endorphin "pain" modulatory system of human beings at spinal level.

A patient with severe bullous emphysema in whom one bulla occupied more than 25% of the hemithorax, with a shift of the mediastinum to the opposite side, was anaesthetised for bullectomy with a combination of intravenous gamma-hydroxybutyric acid and a high thoracic extradural catheter technique. During the operation the patient breathed 100% oxygen through a double-lumen endobronchial tube in the lateral thoracotomy position. Extradural analgesia during the operation was provided by bupivacaine 0.25%, with adrenaline 1:200 000 and, postoperatively, with nicomorphine diluted in dextrose 5%. The advantages of this technique are described.

The influence of indomethacin on the surgical stress response was evaluated in a double-blind study of 20 patients, scheduled for abdominal hysterectomy. The patients were randomly allocated to treatment with either indomethacin, 0.8 mg/kg i.v. preoperatively followed by 100 mg rectally 8-hourly for 3 days (Group I), or placebo (Group P), in both cases supplemented with nicomorphine as needed. Thiopentone was used for induction of anaesthesia, followed by nitrous oxide, enflurane, suxamethonium, and pancuronium. In both groups a significant increase in blood glucose and serum cortisol was seen postoperatively. Twenty-four hours later the values had almost returned to baseline. No differences were found between the absolute increases in the two groups. In both groups the serum concentrations of C-reactive protein, haptoglobin, and orosomucoid increased after an initial small decrease. We conclude that pathways involving prostaglandin synthesis play only a minor role in eliciting the postoperative hyperglycaemic, hypercortisolaemic, and acute phase protein response.

One hundred and sixty-three patients subjected to three different types of thoracic operation were allocated randomly either to balanced intravenous anaesthesia including i.v. opiates with post-operative intramuscular opiates (intramuscular group) or to balanced intravenous anaesthesia without i.v. opiates but with high thoracic epidural regional block during the operation as well as epidural nicomorphine post-operatively (epidural group). Post-operative nicomorphine was given only at the request of the patient and as frequently as needed to obtain satisfactory pain relief. Patients in the epidural group received nicomorphine exclusively by epidural injection. In this paper (Part I), general parameters between the epidural group and the im. group are compared. The epidural group showed acceptable cardiovascular stability during the operation. With the catheter tip at the T3-T4 level, there was apparently a preferential spread downwards of the local anaesthetics. Post-operatively both groups (i.m. and epidural) provided effective and rapid onset of analgesia. There were no major differences in post-operative pain assessment, either by the patient or by the team.

In a randomized double-blind study with flexible dosage, morphine, nicomorphine and pethidine were compared with regard to analgetic effect, dose requirements, dose intervals and adverse reactions. A total of 275 patients were included, and 28 patients were excluded due to adverse reactions (n = 16) and for practical reasons, etc. Acute myocardial infarction (AMI) was diagnosed in about 60% of the patients, and about 30% had ischemic heart disease without AMI. All three analgesics provided equally efficient pain relief in relative doses of morphine 10, nicomorphine 10 and pethidine 75 mg/ml. Severe adverse reactions were few (allergy 3 cases, respiratory insufficiency 4, severe bradycardia 4), whereas nausea was recorded in 20-30%, vomiting in 5-15% and dizziness in 10-30% of the patients, with no difference between the three drugs. Significant blood pressure drop (greater than 30 mmHg) was seen in 3-8% of the patients, with no significant differences between the drugs.

The influence of indomethacin on the need for postoperative analgesics was investigated in a double-blind study of 41 patients scheduled for abdominal hysterectomy. The incidence of side effects was evaluated. The patients were randomly allocated to treatment with either indomethacin, 0.8 mg/kg i.v. preoperatively, followed by 100 mg rectally 8-hourly for 3 days (Group I), or placebo (Group P), in both cases supplemented with nicomorphine as needed. Thiopentone was used for induction of anaesthesia, followed by nitrous oxide, enflurane, suxamethonium, and pancuronium. The average nicomorphine requirement during the study was 14.0 mg/24 h lower in Group I than in Group P. The pain score values were slightly lower in Group I when resting, but similar on movement. A significant increase in perioperative blood loss was found in Group I. Beginning the indomethacin treatment with a preoperative i.v. bolus seems to offer few advantages compared to a purely postoperative regime and may increase the risk of bleeding complications.

In this study the effects of nicomorphine, administered either intramuscularly or by high thoracic epidural route, on the ventilatory and airway occlusion pressure response to CO2 were investigated and compared. Twenty-four patients scheduled for thoracic surgery were allocated randomly to postoperative pain relief by i.m. nicomorphine or by high thoracic epidural nicomorphine. The ventilatory response to 5% carbon dioxide was measured in all patients: first 1 day before operation, secondly on the first day after surgery immediately before nicomorphine administration and finally after the administration, at the moment when no further rise in end-tidal PCO2 (PETCO2) was measured. Respiratory response was assessed in two ways, by measuring minute ventilation (VE) and mouth occlusion pressure (P0.1). There was a significant depression in ventilatory response to CO2 in the intramuscular group (P = 0.03) due to nicomorphine as assessed by the slope of VE vs PETCO2. No significant depression was found in the epidural group, irrespective of measurement of VE or P0.1. No significant shift of apnoeic threshold-PETCO2 was observed in either group.

Treatment with intravenous streptokinase is known to restore blood flow to the ischaemic myocardium in patients with acute myocardial infarction. However, little is known about its effect on chest pain. In a retrospective cohort study, 76 patients treated with streptokinase were compared to 76 patients not treated with streptokinase. All patients had acute myocardial infarction and less than 6 h of cardiac symptoms. Patients treated with streptokinase had a significantly lower need for nicomorphine (median 20 mg) than patients not treated with streptokinase (median 41 mg). Correspondingly, the median duration (3.5 h) of pain was reduced significantly in patients treated with streptokinase compared to patients not treated (24 h). We conclude that intravenous streptokinase given in the acute phase of myocardial infarction is effective in reducing the duration of cardiac chest pain.

• The electrical activity of the stomach and intestine was monitored during the postoperative period in 30 patients who underwent cholecystectomy. All patients received standard general anesthesia with artificial ventilation during operation; some received high epidural analgesia during surgery and postoperatively, and others, fentanyl analgesia during surgery and nicomorphine afterwards. Electroenterography EEnG showed that electrical activity decreased following surgery and returned to base line on the third or fourth day after operation. A marked increase in amplitude and frequency of EEnG oscillations was recorded in 80% of the patients who received bupivacaine injections into the epidural space. A decrease was almost always recorded after nicomorphine injections. During the postoperative period, eating caused a considerable increase in the amplitude and frequency of the electrical activity of the stomach and intestine in patients treated by epidural analgesia, whereas no observable change was recorded in patients treated by nicomorphine injections. It appears that high epidural analgesia may be useful in the treatment of postoperative adynamic ileus. ( Arch Surg 112:580-583, 1977)