Echocardiography and non-invasive imaging in cardiac resynchronization therapy.

The beneficial effects of cardiac resynchronization therapy (CRT) on morbidity and mortality in advanced heart failure patients have been extensively demonstrated. However, previous single- and multicenter studies demonstrated that approximately 30-40% of CRT patients do not show significant clinical improvement or LV reverse remodeling despite fulfilling current inclusion criteria. In search of novel indices that may help to improve the selection of responders to CRT, non-invasive multimodality imaging has provided further insight into the mechanisms underlying CRT response. LV dyssynchrony, extent and location of myocardial scar and LV lead position have shown to be independent determinants of CRT response. An integrated evaluation of these three pathophysiological mechanisms may provide a more accurate selection of heart failure patients who will benefit from CRT and may maximize the cost-effectiveness of this therapy. The present review article provides a critical appraisal of the role of multimodality imaging in the selection of heart failure patients who are candidates for CRT with special focus on the assessment of LV mechanical dyssynchrony, LV myocardial scar tissue extent and LV lead position.

Long-term time-course of nocturnal breathing disorders in heart failure patients.

Some important aspects of clinical manifestations of nocturnal breathing disorders in heart failure (HF) patients are still unknown. We questioned whether the severity of these disorders, first, is stable over time; secondly, shows any systematic trend; and, thirdly, can be predicted over time by a single baseline measurement. We studied 79 stable, optimally treated, moderate-to-severe HF patients who performed a monthly cardiorespiratory recording during 1-yr follow-up. According to their behaviour over time, nocturnal breathing disorders were classified as persistent, absent or occasional. During follow-up, clinically relevant breathing disorders were persistent in approximately 50% of the patients, absent in <20% and occasional in approximately 30%. Increasing/decreasing trends were rarely observed. The positive and negative predictive value of baseline measurement for persistent behaviour over time ranged, respectively, from 71% to 91% and from 91% to 95%, depending on different levels of severity of breathing disorders. A large portion of HF patients experience persistent clinically significant nocturnal breathing disorders over long periods of time. Breathing disorders occur irregularly in about one-third of the patients and are negligible in a minority of them. Rarely do they show a steady increase or decrease over time. A single baseline recording predicts a persistent behaviour with moderate-to-high accuracy.

Alvimopan, a peripherally acting mu-opioid receptor antagonist, compared with placebo in postoperative ileus after major abdominal surgery: results of a randomized, double-blind, controlled study.

BACKGROUND: Alvimopan is a peripherally acting mu-opioid receptor (PAM-OR) antagonist for accelerating gastrointestinal recovery after surgery. METHODS: Patients undergoing open laparotomy (bowel resection, n = 418; hysterectomy, n = 197) were randomized to receive alvimopan 6 or 12 mg or placebo orally > or = 2 h before surgery and then b.i.d. until hospital discharge (up to 7 days). The primary efficacy endpoint was time to gastrointestinal (GI) recovery (measured by toleration of solid food and passage of flatus/stool; GI-3). Secondary endpoints included time to GI-2 recovery (toleration of solid food and passage of stool) and hospital discharge order written (DCO). RESULTS: Alvimopan did not significantly accelerate GI-3 compared with placebo [6 mg: hazard ratio (HR) = 1.20, p = 0.080; 12 mg: HR = 1.24, p = 0.038). However, after adjustment for significant covariates (sex/surgical duration), benefits were significant for both doses (6 mg: HR = 1.24, p = 0.037; 12 mg: HR = 1.26, p = 0.028). Alvimopan also significantly accelerated time to GI-2 (6 mg: HR = 1.37, p = 0.008; 12 mg: HR = 1.33, p = 0.018) and DCO (6 mg: HR = 1.31, p = 0.008; 12 mg: HR = 1.28, p = 0.015). Adverse events were similar between groups. CONCLUSIONS: Alvimopan (6 or 12 mg) accelerates GI recovery and is well tolerated in patients undergoing open laparotomy.

Rapacuronium: first experience in clinical practice.

Rapacuronium is a new non-depolarizing relaxant with a fast onset and rapid recovery. It was approved for the market in the United States in August 1999. The reasons for its acceptance in practice and the niche it fills are the subject of this review. Rapacuronium has been accepted wherever rapid onset and short duration of action are advantageous. It has received the greatest acceptance in brief outpatient procedures that require tracheal intubation. The average time of recovery to a train-of-four ratio of 80% is about 25 min after a usual intubating dose of 1.5 mg kg-1, when block is reversed. Its rapid onset has led some to use it in rapid-sequence induction, but the exact place in this scenario is still being defined. Its spontaneous recovery is rapid enough that many practitioners do not reverse the block if the procedure is long enough. Data suggest that this is reasonable after 60 min and may even be earlier, even 30 min, if verified by monitoring. The main adverse effects of rapacuronium are bronchospasm, hypotension and tachycardia. Of these, only bronchospasm has had significant clinical impact. These effects are dose related and the recommended dose of 1.5 mg kg-1 may keep problems to a minimum. Because rapacuronium is a new drug with unique properties its use gradually increased in its first year. Because of the problems associated with succinylcholine, rapacuronium may have advantages for brief outpatient procedures and in cases where rapid termination of block is desired, provided its adverse effects can be minimized.

Evaluation of neuromuscular and cardiovascular effects of two doses of rapacuronium (ORG 9487) versus mivacurium and succinylcholine.

BACKGROUND: This study compares the neuromuscular blocking and cardiovascular effects of rapacuronium (ORG 9487), a new aminosteroid nondepolarizing muscle relaxant, to recommended intubating doses of succinylcholine and mivacurium. METHODS: Adult patients were randomized in an open-label fashion to receive 1-5 microg/kg fentanyl before 1.5 mg/kg propofol induction followed by 1.5 or 2.5 mg/kg rapacuronium, 1.0 mg/kg succinylcholine, or 0.25 mg/kg mivacurium (i.e., 0.15 mg/kg followed by 0.1 mg/kg 30 s later). RESULTS: Patient neuromuscular blockade status was monitored by measuring the train-of-four response to a supramaximal stimulus at the ulnar nerve every 12 s. Percentage of the first twitch of the train-of-four (T1) at 60 s was similar in patients receiving 1.5 mg/kg rapacuronium, 2.5 mg/kg rapacuronium, and succinylcholine and was significantly less than in patients in the mivacurium group (26, 16, and 18%, respectively, vs. 48%; P < 0.01). Times to 80% T1 depression were also similar among patients in the 1.5 mg/kg rapacuronium, 2.5 mg/kg rapacuronium, and succinylcholine groups and significantly longer in the mivacurium group (62, 54, and 54 s, respectively, vs. 112 s; P < 0.01). Clinical duration was longer in all groups compared with the succinylcholine group; however, clinical duration in the 1.5 mg/kg rapacuronium group was shorter compared with the mivacurium group (15 vs. 21 min, respectively; P < 0.01). Heart rate changes were mild in the 1.5 mg/kg rapacuronium, succinylcholine, and mivacurium groups. The patients in the 2.5 mg/kg rapacuronium group had significantly higher heart rates compared with patients in the mivacurium group. No differences were found in blood pressure changes among patients in the four groups. CONCLUSIONS: Rapacuronium, 1.5 and 2.5 mg/kg, produced neuromuscular blockade as rapidly as succinylcholine and significantly faster than mivacurium. Although succinylcholine continued to show the shortest duration, 1.5 mg/kg rapacuronium used a rapid onset and a relatively short duration and may be considered an alternative to succinylcholine.

Performance deficits following failure: learned helplessness or self-esteem protection?

We report two laboratory experiments which compare two competing explanations of performance deficits following failure: one based on Seligman's learned helplessness theory (LHT), and the other, on self-esteem protection theory (SEPT). In both studies, participants (Study 1: N = 40 pupils from secondary schools in Walbrzych, Poland; Study 2: N = 45 students from the University of Bielefeld, Germany) were confronted with either success or failure in a first phase of the experiment. Then, in the second phase of the experiment the participants had to work on a set of mathematical problems (Study 1) or a set of tasks taken from Raven's Progressive Matrices (Study 2) either privately or in public. In both studies failure in the first phase causes performance deficits in the second phase only if the participants had to solve the test tasks in public. These results were interpreted in line with SEPT and as incompatible with LHT.

Remifentanil versus alfentanil in a balanced anesthetic technique for total abdominal hysterectomy.

STUDY OBJECTIVES: To compare the intraoperative effects and recovery characteristics of remifentanil hydrochloride and alfentanil when administered as part of balanced anesthesia, and to assess the effects of an additional remifentanil infusion administered as analgesic pretreatment before removal of the uterus. DESIGN: Multicenter, double-blind, randomized, parallel-group study. SETTING: Two university hospitals. PATIENTS: 35 ASA physical status I, II, and III women scheduled for elective total abdominal hysterectomy with general endotracheal anesthesia. INTERVENTIONS: Patients were premedicated with midazolam 0.05 mg/kg intravenously (i.v.). Anesthesia was induced with thiopental 2 mg/kg, vecuronium 0.15 mg/kg, and a single dose of opioid over 60 seconds (Pump 1): remifentanil 2 micrograms/kg (Remi/Placebo and Remi/Remi groups) or alfentanil 50 micrograms/kg (Alf/Placebo group). Anesthesia was maintained with a nitrous oxide/oxygen mixture (66:34 ratio) and a continuous opioid infusion: remifentanil 0.25 microgram/kg/min (Remi/Placebo and Remi/Remi) or alfentanil 0.5 microgram/kg/min (Alf/Placebo). At skin incision, a second blinded drug infusion was also initiated (Pump 2): remifentanil 0.25 microgram/kg/min (Remi/Remi) or saline placebo (Remi/Placebo and Alf/Placebo). Intraoperative responses were controlled with single doses of opioid and/or rate titrations via Pump 1. Pump 2 was terminated on removal of the uterus. Pump 1 was terminated at skin closure. MEASUREMENTS AND MAIN RESULTS: The mean (+/- SD) opioid infusion rates administered for the duration of Pump 2 to suppress responses to removal of the uterus were 0.49 +/- 0.27 microgram/kg/min, 1.99 +/- 1.34 micrograms/kg/min, and 0.49 +/- 0.07 microgram/kg/min for the Remi/Placebo, Alf/Placebo, and Remi/Remi groups, respectively. At these rates, similar proportions of patients in the Remi/Placebo (67%) and the Alf/Placebo (60%) groups had responses. Fewer patients had responses in the Remi/Remi group (8%) compared with the Remi/Placebo and Alf/Placebo groups (p < 0.05). The mean total opioid doses used during maintenance were 84.6 micrograms/kg (Remi/Placebo), 393 micrograms/kg (Alf/Placebo), and 68.7 micrograms/kg (Remi/Remi). Awakening times were significantly shorter (p < 0.05) in the remifentanil population compared with the alfentanil population, but discharge times were similar. More patients received naloxone to reverse opioid effects in the alfentanil population (60%) than in the remifentanil population (20%) (p < 0.05). CONCLUSIONS: A mean remifentanil infusion of 0.49 microgram/kg/min is as effective as a mean alfentanil infusion of 1.99 micrograms/kg/min in suppressing intraoperative responses. Doubling of the remifentanil infusion to 0.5 microgram/kg/min before the major stress event improves suppression of responses and lowers intraoperative use of remifentanil without prolonging recovery times. Remifentanil allows faster awakening times than alfentanil, but preemptive administration of postoperative analgesics is recommended to facilitate discharge.

The safety and efficacy of oral transmucosal fentanyl citrate for preoperative sedation in young children.

Oral transmucosal fentanyl citrate (OTFC) is a labeled preoperative pediatric sedative. Doses greater than 15 micrograms/kg are associated with a high incidence of post-operative nausea and vomiting and occasional respiratory depression. We studied the safety and efficacy of OTFC in children 6 yr old and younger at a dose of 15 micrograms/kg. Nineteen patients undergoing surgery associated with postoperative pain were randomized to receive OTFC/intravenous (IV) saline or placebo lozenge/IV fentanyl. After 45 min, patients receiving OTFC became more sedated than the placebo group, but there were no differences in cooperation, apprehension, parental separation, or induction cooperation scores. Preoperatively, neither respiratory depression nor oxygen desaturation occurred. Nine of 10 OTFC patients developed mild pruritus, and three of 10 OTFC patients vomited preoperatively; neither complication occurred in the placebo group. (The high incidence of preoperative vomiting led to the termination of the protocol before the anticipated enrollment of 40 patients.) General anesthesia was induced via a mask, followed by a propofol infusion. Spo2 and respiratory rate were monitored, and sedation, apprehension, cooperation, ease of parental separation, and induction cooperation were scored. One OTFC patient developed rigidity during induction. Emergence and recovery were not delayed by OTFC despite a 50% incidence of postoperative vomiting. We do not recommend the use of OTFC in a 15 micrograms/kg dose as a routine preoperative sedative in children 6 yr old and younger.

Efficacy and safety of divided dose administration of mivacurium for a 90-second tracheal intubation.

STUDY OBJECTIVE: To compare the safety and effectiveness of 0.25 mg divided doses of mivacurium chloride to succinylcholine for a 90-second tracheal intubation. DESIGN: Randomized, double-blind, multicenter study in two groups. SETTING: Operating rooms at four university medical centers. PATIENTS: 200 healthy ASA status I and II adult patients scheduled for elective surgery with general anesthesia and endotracheal intubation. INTERVENTIONS: Patients were premedicated with 1 to 2 mg midazolam and 2 micrograms/kg fentanyl. Anesthesia was induced with 2 mg/kg propofol. Group A received 0.25 mg/kg mivacurium given as a divided dose (0.15 mg/kg followed in 30 seconds with 0.1 mg/kg). Group B (control) received 1.5 mg/kg succinylcholine (SCh) preceded two minutes earlier by 50 micrograms/kg d-tubocurarine (dtc). MEASUREMENTS AND MAIN RESULTS: Tracheal intubation grading, train-of-four response of the adductor pollicis, heart rate (HR), and mean arterial blood pressure (MAP) were measured and evaluated. Chi-square analysis was performed for comparison between Group A and Group B with respect to the frequency distribution of intubation using the scores excellent, good, and poor and not possible (combined). Group B had a significantly higher excellent score of intubation than Group A, 84% versus 56% (p < 0.0001). No significant difference was found between the two groups when the scores excellent and good were combined (Fisher's Exact test, p = 0.28). The changes in MAP and HR were similar for the two groups. CONCLUSIONS: When Sch is not desirable, mivacurium 0.25 mg/kg given as a divided dose provides good to excellent intubation conditions 90 seconds after the initial dose without significant changes in MAP or HR. It can be an appropriate alternative for short surgical procedures. It must be emphasized that this conclusion does not apply to rapid-sequence induction-intubation.

Rocuronium onset of action: a comparison with atracurium and vecuronium.

The onset, maximal neuromuscular block, and duration of rocuronium were compared with atracurium and vecuronium during enflurane anesthesia. Sixty patients received rocuronium (80, 100, 120, or 160 micrograms/kg). Enflurane enhanced a rocuronium neuromuscular block in a dose-related manner; the ED50 was 104 +/- 11 and 83 +/- 7 micrograms/kg (SEM) during 1% and 2% enflurane anesthesia, respectively. Patients receiving atracurium (0.12 mg/kg) or vecuronium (0.02 mg/kg) were studied during 1% enflurane anesthesia until seven in each group qualified by achieving a maximal block between 85% and 97%. These patients were matched with each other and with patients who had received rocuronium. Seven groups of three patients (rocuronium, vecuronium, and atracurium) were obtained. The average difference in maximal block was less than 2% between matched patients. The ratio of dose used to achieve a similar final block suggests potency ratios of 1, 8.5, and 1.2 for rocuronium, vecuronium, and atracurium. Rocuronium's onset time (time from drug administration to 50%, 75%, and 90% of final block) was significantly faster than either of the other two muscle relaxants (P < 0.01). Time to 90% of final block was 1.35 min for rocuronium, 3.06 min for atracurium, and 3.71 min for vecuronium. Using these equipotent doses, atracurium also had a shorter time to develop neuromuscular block than vecuronium (P < 0.05). For these three intermediate duration neuromuscular blockers, speed of onset was inversely related to their potency, confirming a relationship that had been demonstrated for the long-acting drugs pancuronium, d-tubocuranine, and gallamine.

A comparison of desflurane and isoflurane in prolonged surgery.

STUDY OBJECTIVE: To compare desflurane with isoflurane in several anesthetic situations. DESIGN: Intubating conditions, hemodynamic response to intubation, maintenance hemodynamics, and speed of recovery from desflurane and isoflurane anesthesia were evaluated. In addition, interaction with a muscle relaxant at low and high concentrations of the anesthetics were compared. SETTING: Thomas Jefferson University Hospital. PATIENTS: Thirty-two patients who received general anesthesia for lengthy, mostly orthopedic procedures. INTERVENTIONS: Immediately after induction with thiopental sodium, desflurane or isoflurane in nitrous oxide-oxygen was administered via face mask. Anesthesia was deepened until end-tidal concentration reached 1.7 minimum alveolar concentration (MAC). The trachea was intubated without the aid of a muscle relaxant. Heart rate (HR) and blood pressure (BP) were recorded before and at 1, 2, 4, 5, and 10 minutes after intubation. Noninvasive cardiac output (CO) and systemic vascular resistance (SVR) were determined while the patient was awake, immediately before intubation, and at 5 and 10 minutes after intubation. Following intubation, the concentration of desflurane or isoflurane was lowered until the end-tidal concentration reached 0.65 MAC (low-MAC group), 1.25 MAC (high-MAC group), or 0 MAC (control group). Pancuronium bromide in 0.005 mg/kg doses was administered incrementally until T1 (first twitch of train-of-four) was depressed more than 90%. ED50 and ED95 for pancuronium with balanced anesthesia and for desflurane or isoflurane in low and high MACs, as well as speed of recovery, were determined. The time to responsiveness and awakening also was determined. MEASUREMENTS AND MAIN RESULTS: There was no significant difference between desflurane and isoflurane in intubating conditions or in BP or HR response to tracheal intubation. Both anesthetics increased HR significantly during induction. BP rose with desflurane at the preintubation point; other points showed no difference. A hyperdynamic response of increased HR and BP above 20% of baseline values was seen more frequently with desflurane (n = 7) than with isoflurane (n = 1). CO was elevated at all times after induction for low and high concentrations of both drugs, while SVR decreased over the same time with no significant difference between drugs. ED50 and ED95 for pancuronium were similar under desflurane and isoflurane at both low and high MAC, but they were significantly lower than under balanced anesthesia. Awakening times were similar for desflurane and isoflurane. CONCLUSIONS: Desflurane is similar to isoflurane in providing anesthesia for intubation and maintenance. Desflurane tends to increase HR and occasionally causes a hyperdynamic response during rapid deepening of anesthesia. It is very similar to isoflurane in its interaction with pancuronium.

Right ventricular myocardial protection through intracavitary cooling in cardiac operations.

In an attempt to protect the right ventricle, we designed and tested a closed cooling system that circulates cold saline through a double-lumen, balloon-tipped catheter positioned in the right ventricular cavity. Fourteen sheep were randomly assigned to two groups. In group A (n = 7), the right ventricular cooling catheter system was used in addition to coronary cardioplegic perfusion and systemic hypothermia for myocardial protection. Group B (n = 7) served as a control group. In group A, the right ventricular temperatures were significantly lower than those of the control group (16.1 degrees +/- 0.3 degrees C versus 23.9 degrees +/- 0.4 degrees C; p less than 0.0001, Student's t test). The most common temperature range was 12 degrees to 18 degrees C (67.1%, frequency distribution analysis), and 63.2% of temperatures were below 16 degrees C. The catheter system also maintained the temperatures of the interventricular septum at a lower level than those recorded in the control group and prevented septal rewarming, which was significant in group B (from 16.5 degrees +/- 1.5 degrees C to 25.0 degrees +/- 0.9 degrees C; p less than 0.04, Mann-Whitney U test). Left ventricular temperatures were not changed by the catheter system. By better cooling the right ventricle and the septum, the right ventricular cooling catheter system should decrease the prevalence of right ventricular failure and allow more time to safely complete multiple coronary anastomoses in coronary artery bypass graft operations.

Glutamine and smooth muscle morphology of the gut in rats on total parenteral nutrition.

The purpose of this study was to assess the effects of addition of L-glutamine to an IV nutritional solution on the urinary excretion of 3-methylhistidine (3-MeH) and the morphology of the musculature of the gut in rats. Two experiments were run. In experiment 1 glutamine was added to a mildly hypocaloric IV solution which contained no other amino acids. For experiment 2 glutamine was added to an isocaloric balanced amino acid mixture. In both experiments L-alanine was added in equimolar amounts in place of the L-glutamine for the control groups. Providing glutamine in an IV diet without other amino acids significantly decreased urinary 3-MeH excretion (p less than 0.05). Electron microscopy and morphometric analysis of the jejunum showed an approximate 50% loss of musculature from the gut wall in alanine-treated animals. Glutamine supplementation of a balanced amino acid regime had no effect on urinary 3-MeH excretion or the musculature of the jejunum. We concluded that (1) glutamine is a preferred fuel for jejunal smooth muscle as well as for mucosal cells of the jejunum and (2) only when amino acids are limiting does exogenous glutamine prevent atrophy of the gut musculature.