Preliminary UK experience of dexmedetomidine, a novel agent for postoperative sedation in the intensive care unit

Dexmedetomidine, a highly selective and potent alpha2-adrenergic agonist, has a potentially useful role as a sedative agent in patients requiring intensive care. As part of a larger European multicentre trial, a total of 119 postoperative cardiac and general surgical patients requiring ventilation and sedation in an intensive care unit were enrolled in four centres in the United Kingdom. One hundred and five patients were randomly allocated to receive either dexmedetomidine or placebo with rescue sedation and analgesia provided by midazolam and morphine, respectively. Compared with the control group, intubated patients receiving dexmedetomidine required 80% less midazolam [mean 4.9 (5.8) microg.kg-1.h-1 vs. 23.7 (27.5) microg.kg-1.h-1, p < 0.0001], and 50% less morphine [11.2 (13.4) microg.kg-1.h-1 vs. 21.5 (19.4) microg.kg-1.h-1,p = 0.0006]. Cardiovascular effects and adverse events could be predicted from the known properties of alpha-2 agonists. In conclusion, dexmedetomidine is a useful agent for the provision of postoperative analgesia and sedation.     

Preliminary experience with the 1.32 μm neodymium-YAG laser in the treatment of tracheobronchial malignancy

Endoscopic laser treatment for tracheobronchial malignancy is usually given with the neodymium-YAG laser using the 1.064m output beam. However, recent experimental work suggests that the 1.32m output beam of this laser has more desirable tissue effects. We have now treated 55 patients with the 1.32m Nd-YAG laser (MBB-Medizintechnic) under general anaesthesia, using power settings of 10–20 W and pulse durations of up to 1 s. The indications for treatment were localized airway obstruction in each case. Airway calibre was improved in 46 (84%) patients and this was associated with an improvement in symptoms of cough and breathlessness. Patients with tracheal and carinal obstruction exhibited the most striking clinical improvements with up to four-fold increases in peak expiratory flow. In patients with more peripheral endobronchial obstruction, treatment improved airway calibre less frequently and resulted in a smaller clinical improvement. Of 11 patients with obstruction of a main bronchus and lung collapse, treatment led to partial or complete re-expansion in 10 cases (91%). The 1.32m wavelength allows treatment to be conducted efficiently and safely but at a considerably lower power than is required for the 1.064mwavelength. The ability to use low powers has the apparent advantage of generating only negligible quantities of smoke. Our experience with this new laser system demonstrates its considerable potential in the management of tracheobronchial malignancy.     

Factors determining the duration of tracheal intubation in cardiac surgery: a single-centre sequential patient audit

BACKGROUND AND OBJECTIVE: The study was designed to identify those factors associated with early tracheal extubation following cardiac surgery. Previous studies have tended to concentrate on surgery for coronary artery bypass or on other selected cohorts. METHODS: Sequential cohort analysis of 296 unselected adult cardiac surgery patients was performed over 3 months. RESULTS: In total, 39% of all patients were extubated within 6 h, 89% within 24 h and 95% within 48 h. Delayed extubation (>6 h after surgery) appeared unrelated to age, gender, body mass index, a previous pattern of angina or myocardial infarction, diabetes, preoperative atrial fibrillation, and preoperative cardiovascular assessment, as well as other factors. Delayed tracheal extubation was associated with poor left ventricular, renal and pulmonary function, a high Euroscore, as well as the type, duration and urgency of surgery. Early extubation (<6 h) was not associated with a reduced length of stay in either the intensive care unit or in hospital compared with patients who were extubated between 6 and 24 h. In these groups, it is presumed that organizational and not clinical factors appear to be responsible for a delay in discharge from intensive care. Patients who were extubated after 24 h had a longer duration of hospital stay and a greater incidence of postoperative complications. Postoperative complications were not adversely affected by early tracheal extubation. CONCLUSIONS: In an unselected sequential cohort, both patient- and surgery-specific factors may be influential in determining the duration of postoperative ventilation of the lungs following cardiac surgery. In view of the changing nature of the surgical population, regular re-evaluation is useful in reassessing performance.     

Hemodynamic effects of atracurium, vecuronium and pancuronium during sufentanil anesthesia for coronary artery bypass

A study was undertaken to evaluate the cardiovascular effects of sufentanil, in combination with three different muscle relaxants, used as sole anesthetic with 100% O2 in 30 patients undergoing elective coronary artery vein graft surgery. Patients were randomly allocated to receive pancuronium (P), vecuronium (V) or atracurium (A) for muscle relaxation. All patients received 15 micrograms/kg sufentanil at induction followed by 5-10 micrograms/kg sufentanil prior to sternotomy. At the 95% level of significance no statistical difference was found for any of the measured and derived cardiovascular parameters between groups P, V and A, except for a decreased systolic blood pressure in the atracurium group after induction. Sufentanil in combination with pancuronium or vecuronium provided stable hemodynamic conditions throughout anesthesia. Atracurium was less satisfactory. We conclude that there is no advantage to be gained, in the presence of beta blockade, from the use of the new generation muscle relaxants as compared to pancuronium during high-dose sufentanil anesthesia for coronary artery vein grafting.     

Efficacy and safety of the cyclooxygenase 2 inhibitors parecoxib and valdecoxib in patients undergoing coronary artery bypass surgery

OBJECTIVE: Inhibition of cyclooxygenase 2 provides analgesia in ambulatory patients. We prospectively evaluated the safety and efficacy of a newly introduced cyclooxygenase 2 inhibitor in patients undergoing coronary artery bypass grafting surgery through a median sternotomy in a randomized clinical trial. METHODS: A total of 462 patients with New York Heart Association classes I to III who were less than 77 years of age and were from 58 institutions in the United States, Canada, Germany, and the United Kingdom participated in this multicenter, phase III, placebo-controlled, double-blind, randomized, parallel-group trial. Patients were allocated at a ratio of 2:1 to parecoxib/valdecoxib or standard care (control) groups, respectively. Intravenous study drug (40 mg) was administered within 30 minutes after extubation and every 12 hours for a minimum of 3 days. Subsequently, oral treatment at a dose of 40 mg every 12 hours was initiated and administered for a combined total of 14 days. Patient-controlled analgesia with morphine, oral opioids, or acetaminophen was available as required. Assessment of the analgesic efficacy of the study drug was primarily based on morphine and morphine equivalent use. Additional efficacy evaluations included daily pain intensity, patient and physician global evaluation of study medication, and pain effect on quality of life. Clinical adverse events were assessed by the principal investigator at each site from the time of the first dose through the 30-day postdosing period. RESULTS: Patients in the parecoxib/valdecoxib group received significantly less morphine or morphine equivalents than patients in the control group during the 0- to 24-hour (P =.009), 24- to 48-hour (P =.017), 72- to 96-hour (P =.002), 96- to 120-hour (P =.004), and 120- to 144-hour (P =.037) periods. Both patients (P <.001) and physicians (P <.001) evaluated the study medication as significantly better than control therapy. The modified Brief Pain Inventory questionnaire used in the oral dosing period detected significant improvements in the parecoxib/valdecoxib treatment group in 6 of 8 domains tested (eg, current pain, worst pain, and mood) beginning on day 4 and continuing for at least 4 days. Although there were no differences between the groups in overall adverse events, serious adverse events occurred twice as frequently in parecoxib/valdecoxib-treated patients (19.0%, 59/311 patients) than in control patients (9.9%, 15/151 patients; P =.015). Regarding individual serious adverse events, a greater incidence in sternal wound infection was found in the parecoxib/valdecoxib patients (10 [3.2%]) versus control patients (0 [0%]) (P =.035). The incidences of other individual serious adverse events, including cerebrovascular complications, myocardial infarction, and renal dysfunction, were proportionally greater but not significantly different between the groups. CONCLUSIONS: In patients undergoing coronary artery bypass grafting surgery, the cyclooxygenase 2 inhibitor combination, parecoxib/valdecoxib, was effective for postoperative analgesia. However, the 14-day treatment regimen also was associated with an increased incidence of serious adverse events overall and sternal wound infections in particular. Therefore our study raises important concerns requiring their comprehensive evaluation in a large-scale trial before these cyclooxygenase 2 inhibitors are used in patients undergoing coronary artery bypass grafting surgery.     

Effects of the inotrope DPI 201-106 on cardiac performance following cardiac surgery

The haemodynamic, cardiac metabolic and electrocardiographic effects of the intravenous inotropic agent DPI 201-106, in 20 and 40 milligram doses, were studied in patients after coronary arterial bypass grafting. The patients were randomly allocated to receive placebo or DPI 201-106. Those receiving the active drug received either the 20 or the 40 milligram dosages of DPI 201-106. Both the placebo and the active drug were infused over 20 minute periods. Two baseline readings confirmed haemodynamic stability, and readings were taken immediately following the infusions and then at 20 minutes and at 40 minutes afterwards. Comparison of all the haemodynamic and metabolic data did not reveal any significant intra or inter group differences. Comparison of the electrocardiographic data revealed some differences. Patients receiving DPI 201-106 showed prolongation of the QTc interval immediately following the infusions. Changes in ST segments and T waves were observed. Independent analysis of the affected electrocardiographs reported that the changes were suggestive of, but not pathognomonic of, myocardial ischaemia. The metabolic data showed that the electrocardiographic changes were not associated with any evidence of anaerobic metabolism. The indication for DPI 201-106 as a positive inotropic agent in patients following coronary revascularization surgery was not established.     

Intravenous milrinone following cardiac surgery: I. Effects of bolus infusion followed by variable dose maintenance infusion. The European Milrinone Multicentre Trial Group.

The hemodynamic and adverse effects of intravenous milrinone were studied in 99 adult patients (66 men) following elective myocardial revascularization, mitral and/or aortic valve surgery. All patients had a low cardiac output (cardiac index [CI] mean 1.93, range, 1.11 to 2.5 L/min/m2) despite adequate cardiac filling pressure (mean pulmonary capillary wedge pressure [PCWP] 11.5 mmHg, range, 8 to 20 mmHg). Following a period of baseline stability (mean 17.8 minutes, range, 10 to 50 minutes), patients received a bolus infusion of 50 micrograms/kg over 10 minutes. A continuous maintenance infusion of 0.375 (low), 0.5 (mid) or 0.75 (high) micrograms/kg/min was administered for a minimum of 12 hours. Patients were allocated to each dosage group sequentially, not randomly. Hemodynamic measurements were made before the start of milrinone and 15 minutes after the bolus infusion. Further measurements were made at 30, 45, and 60 minutes, and at 3, 6, and 12 hours after the start of treatment. Measurements were also made at 2 and 4 hours after treatment was stopped. The bolus infusion caused significant increases in CI, heart rate (HR), and stroke index (SI), (P < 0.001), and significant falls in PCWP, right atrial pressure (RAP), mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), mean arterial pressure (MAP), and systemic vascular resistance (SVR) (P < 0.001). These effects were maintained to a significant degree by each of the three maintenance infusion regimens, although the pulmonary vasodilator effects appeared less predictable and more dose dependent. Eighteen patients (19%) had arrhythmias; 16 of these were judged not to be serious events. Two were deemed serious; these were both episodes of fast atrial fibrillation (AF).(ABSTRACT TRUNCATED AT 250 WORDS)