Does Low-dose Droperidol Administration Increase the Risk of Drug-induced QT Prolongation and Torsade de Pointes in the General Surgical Population?
Eckerman, Karen M. C.R.N.A. M.N.A. ; Jacob, Kelly A. C.R.N.A. M.N.A. ; Pawlaski, Erin M. C.R.N.A. M.N.A. ; Wigersma, Susan K. C.R.N.A. M.N.A. ; Marienau, Mary E. Shirk C.R.N.A., M.S. ; Oliver, William C. M.D. ; Narr, Bradly J. M.D. ; Ackerman, Michael J. M.D., Ph.D.
Anesthesiology. 107(4):531-536, October 2007. Nuttall, Gregory A. M.D.

Background: The US Food and Drug Administration issued a black box warning regarding the use of droperidol and the potential for torsade de pointes (TdP).
Methods: The primary objective of this retrospective study was to determine whether low-dose droperidol administration increased the incidence of TdP in the general surgical population during a 3-yr time period before and after the Food and Drug Administration black box warning. A random sample of 150 surgical patients during each time interval was selected to estimate the droperidol use for each time period.
Results: During the time period before the black box warning (July 1, 1998 to June 30, 2001), 2,321/139,932 patients (1.66%) had QT prolongation, TdP, or death within 48 h after surgery. We could identify no patients who clearly developed TdP before the black box warning. There was one patient for whom the cause of death could not positively be ruled out as due to TdP. In the time period after the black box warning (July 1, 2002 to June 30, 2005), 2,207 patients (1.46%) had documented QT prolongation, TdP, or death within 48 h after surgery, including only two cases (<0.1%) of TdP. The incidence of droperidol exposure was approximately 12% (exact 95% confidence interval, 7.3-18.3%) before the black box warning and 0% after placement of the black box warning on droperidol. Therefore, we estimate that approximately 16,791 patients (95% confidence interval, 10,173-25,607) were exposed to droperidol, none of whom experienced documented TdP.
Conclusions: This indicates that the Food and Drug Administration black box warning for low dose droperidol is excessive and unnecessary.

Effects of Age and Emotionality on the Effectiveness of Midazolam Administered Preoperatively to Children.
Clinical Investigations
Kain, Zeev N. M.D., M.B.A. ; MacLaren, Jill Ph.D. ; McClain, Brenda C. M.D. ; Saadat, Haleh M.D. ; Wang, Shu-Ming M.D. ; Mayes, Linda C. M.D. ; Anderson, George M. Ph.D. 
Anesthesiology. 107(4):545-552, October 2007.

Abstract:
Background: Multiple studies document the beneficial effect of midazolam on preoperative anxiety in children. Many clinicians report, however, that some children may in fact not benefit from the administration of this drug.
Methods: After screening for relevant exclusion criteria, children undergoing surgery were enrolled in the study (n = 262) and received 0.5 mg/kg oral midazolam at 20-40 min before induction of anesthesia. Personality instruments were administered to all children, and anxiety levels were evaluated before and after administration of midazolam as well as during induction of anesthesia. Blood was drawn during the induction process and later analyzed for midazolam levels. A priori definitions of responders and nonresponders to midazolam were established using a multidisciplinary task force, videotapes of induction, and a validated and reliable anxiety scale, the modified Yale Preoperative Anxiety Scale.
Results: While 57% of all children scored at the minimum of the modified Yale Preoperative anxiety scale, 14.1% of children fell in the a priori defined group of midazolam nonresponders. Midazolam blood levels (94 +/- 41 vs. 109 +/- 40 ng/ml) and timing between administration of midazolam and induction (28 +/- 9 vs. 29 +/- 8 min) did not differ between midazolam responders and nonresponders. In contrast, midazolam nonresponders were younger (4.2 +/- 2.3 vs. 5.9 +/- 2.0 yr), more anxious preoperatively (49.7 +/- 22.9 vs. 38.3 +/- 19.1), and higher in emotionality (13.6 +/- 3.6 vs. 11.3 +/- 3.8) as compared with responders (P < 0.05).
Conclusions: Although midazolam is an effective anxiolytic for most children, 14.1% of children still exhibit extreme distress. This subgroup is younger, more emotional, and more anxious at baseline. Future studies are needed to determine the best strategy to treat these children.

ACTA ANAESTHESIOLOGICA SCANDINAVICA - TOP

Effect of 3 g of intravenous paracetamol on post-operative analgesia, platelet function and liver enzymes in patients undergoing tonsillectomy under local anaesthesia
M. Silvanto, E. Munsterhjelm, S. Savolainen, P. Tiainen, T. Niemi, O. Ylikorkala, H. Scheinin, K. T. Olkkola
Acta Anaesthesiologica Scandinavica 2007; 51 (9), 1147–1154.

Background: Paracetamol is often given as an adjunctive analgesic to reduce opioid-related adverse effects but its optimal dose is unknown. We studied the analgesic effect and safety of a single 3-g intravenous (i.v.) dose of paracetamol in adults.
Methods: One hundred and seven patients undergoing tonsillectomy under local anaesthesia were randomly allocated to receive i.v. 3 g of paracetamol, 75 mg of diclofenac or placebo prior to surgery. The consumption of post-operative morphine using a patient-controlled analgesia-device was quantified for 6 h. Platelet aggregation and the concentrations of paracetamol, liver aminotransferases, glutathione transferase alpha 1-1 (GSTA1-1) and thromboxane B2 were measured.
Results: During the first hours after surgery, both paracetamol and diclofenac reduced (P < 0.05) the consumption of morphine but had no effect thereafter. The values for the 6-h cumulative consumption of morphine in patients given paracetamol (18.7 ± 13.8 mg), diclofenac (16.1 ± 9.9 mg) and placebo (22.0 ± 12.1 mg) did not differ. Paracetamol had no effect on platelet aggregation, which was impaired only by diclofenac in response to arachidonic acid (P < 0.005). Both paracetamol (P < 0.01) and diclofenac (P < 0.005) inhibited the release of thromboxane B2 at 1 h but they did not affect serum aminotransferase and GSTA1-1 levels. One patient given paracetamol displayed a transient increase in GSTA1-1 and liver aminotransferases.
Conclusion: During the initial hours after tonsillectomy, the administration of 3 g of i.v. paracetamol and 75 mg of diclofenac reduced the consumption of morphine. Both drugs also reduced the release of thromboxane B2 from activated platelets but only diclofenac had a negative effect on platelet aggregation. In sensitive individuals, large doses of paracetamol may disturb the hepatocellular integrity. We do not recommend the use of i.v. doses of paracetamol higher than 1 g.

Pulse pressure variation as a tool to detect hypovolaemia during pneumoperitoneum
F. Bliacheriene, S. B. Machado, E. B. Fonseca, D. Otsuke, J. O. C Auler Jr, F. Michard
Acta Anaesthesiologica Scandinavica 2007; 51 (9), 1268–1272.

Background: Pulse pressure variation (ΔPP) and systolic pressure variation (SPV) induced by mechanical ventilation have been proposed to detect hypovolaemia and guide fluid therapy. During laparoscopic surgery, chest compliance is decreased by pneumoperitoneum. This may affect the value of SPV and ΔPP as indicators of intravascular volume status. Thereby, we investigated the effects of pneumoperitoneum and hypovolaemia on SPV and ΔPP.
Methods: We measured ΔPP, SPV and the inspiratory (Δup) and expiratory (Δdown) components of SPV, at baseline, during pneumoperitoneum, during pneumoperitoneum and hypovolaemia and after the return to baseline conditions, in 11 mechanically ventilated rabbits. Pneumoperitoneum was induced by inflating the abdomen with carbon dioxide, and hypovolaemia was induced by controlled haemorrhage.
Results: Pneumoperitoneum induced an increase in SPV from 8.5 ± 1.6 to 13.3 ± 2.6 mmHg (+56%, P < 0.05) as a result of an increase in Δup from 2.0 ± 1.0 to 6.7 ± 2.1 mmHg (+236%, P < 0.05), but no significant change in Δdown, nor in ΔPP. Haemorrhage induced a significant (P < 0.05) increase in SPV from 13.3 ± 2.6 to 19.9 ± 3.7 mmHg (+50%), in Δdown from 6.6 ± 3.3 to 14.0 ± 4.9 mmHg (+112%) and in ΔPP from 11.1 ± 4.8 to 24.9 ± 9.8% (+124%) but no change in Δup. All parameters returned to baseline values after blood re-infusion and abdominal deflation.
Conclusions: SPV is modified by haemorrhage but it is also influenced by pneumoperitoneum. In contrast, ΔPP is modified by haemorrhage but not by pneumoperitoneum. These findings suggest that ΔPP should be used preferentially instead of SPV to detect hypovolaemia and guide fluid therapy during laparoscopic surgery.

BRITISH JOURNAL OF ANAESTHESIA - TOP

Sciatica: a review of history, epidemiology, pathogenesis, and the role of epidural steroid injection in management
M. A. Stafford, P. Peng and D. A. Hill
British Journal of Anaesthesia 2007; 99(4):461-473

Radicular pain in the distribution of the sciatic nerve, resulting from herniation of one or more lumbar intervertebral discs, is a frequent and often debilitating event. The lifetime incidence of this condition is estimated to be between 13% and 40%. Fortunately, the majority of cases resolve spontaneously with simple analgesia and physiotherapy. However, the condition has the potential to become chronic and intractable, with major socio-economic implications. This review discusses the history, epidemiology, pathophysiology, and natural history of sciatica. A Medline search was performed to obtain the published literature on the sciatica, between 1966 and 2006. Hand searches of relevant journals were also performed. Epidemiological factors found to influence incidence of sciatica included increasing height, age, genetic predisposition, walking, jogging (if a previous history of sciatica), and particular physical occupations, including driving. The influence of herniated nucleus pulposus and the probable cytokine-mediated inflammatory response in lumbar and sacral nerve roots is discussed. An abnormal immune response and possible mechanical factors are also proposed as factors that may mediate pain. The ongoing issue of the role of epidural steroid injection in the treatment of this condition is also discussed, as well as potential hazards of this procedure and the direction that future research should take.

Postoperative nausea, vomiting, airway morbidity, and analgesic requirements are lower for the ProSeal laryngeal mask airway than the tracheal tube in females undergoing breast and gynaecological surgery
M. Hohlrieder, J. Brimacombe, A. von Goedecke and C. Keller
British Journal of Anaesthesia 2007; 99(4):576-580

Background: We test the hypothesis that the frequency of postoperative nausea and vomiting is similar for the ProSeal laryngeal mask airway (LMA) and the tracheal tube.
Methods: Two hundred consecutive female patients (ASA I–II, 18–75 yr) undergoing routine breast and gynaecological surgery were divided into two equal-sized groups for airway management with the ProSeal LMA or tracheal tube.
Results: Ventilation was better and airway trauma less frequent for the ProSeal LMA. For the ProSeal group, the time spent in the post-anaesthesia care unit was shorter (69 vs 88 min, P < 0.0001); fewer doses of tropisetron were required in the post-anaesthesia care unit (P 0.001) and ward (P = 0.004); morphine requirements were lower in the post-anaesthesia care unit (6.0 vs 8.1 mg, P = 0.005) and ward (6.1 vs 8.9, P = 0.004); nausea was less frequent at all times (overall: 13% vs 53%, P < 0.0001); vomiting was less frequent at 2 h (4% vs 18%, P = 0.003) and 24 h (5% vs 19%, P = 0.004); and sore throat was less frequent at all times (overall: 12% vs 38%, P < 0.0001).
Conclusions: The ProSeal LMA reduced the absolute risk of postoperative nausea and vomiting by 40% (53–13%). In patients without the need for morphine, the ProSeal LMA reduced the absolute risk of postoperative nausea and vomiting by 23% (37–14%). We conclude that the frequency of postoperative nausea, vomiting, airway morbidity, and analgesic requirements is lower for the ProSeal LMA than the tracheal tube in females undergoing breast and gynaecological surgery.

Effect of total intravenous anaesthesia and balanced anaesthesia on the frequency of coughing during emergence from the anaesthesia
M. Hohlrieder, W. Tiefenthaler, H. Klaus, M. Gabl, P. Kavakebi, C. Keller and A. Benzer
British Journal of Anaesthesia 2007; 99(4):587-591

Background: The effects of total intravenous anaesthesia (TIVA) and balanced anaesthesia (BAL) on coughing during emergence from the general anaesthesia have not yet been compared.
Methods: Fifty patients, aged 18–60 yr, undergoing elective lumbar disk surgery were randomly allocated to undergo TIVA (propofol–remifentanil) or BAL (fentanyl–nitrous oxide–sevoflurane). Extubation was performed in the knee–elbow position, documented on video, and subsequently evaluated by blinded examiners.
Results: There was no difference between TIVA and BAL patients with respect to patient characteristics, proportion of smokers, surgical time, or time of emergence. The median number of coughs was significantly lower in the TIVA group (1, range 0–9) than in the BAL group (4, range 0–20, P = 0.007). Mean maximal heart rate and mean maximal arterial pressure measured during emergence were also significantly lower in the TIVA group (P = 0.009 and P = 0.006, respectively).
Conclusions: During emergence from anaesthesia in the knee–elbow position, TIVA is associated with significantly less coughing and reduced haemodynamic response when compared with BAL.

Laryngeal exposure during laryngoscopy is better in the 25° back-up position than in the supine position
B. J. Lee, J. M. Kang and D. O. Kim
British Journal of Anaesthesia 2007; 99(4):581-586

Background: Good visualization of the glottis is important for tracheal intubation. This study evaluated whether the 25° back-up position improves the quality of the laryngeal view during laryngoscopy.
Methods: Laryngoscopy with a curved blade was performed on 40 anaesthetized patients. The patients were randomly assigned to two groups. Laryngeal views were captured with a rigid 0° endoscope. Views were recorded for each patient in Group A (n = 20) during laryngoscopies performed with the patient lying first in the supine position and then in the 25° back-up position. Laryngeal views for patients in Group B (n = 20) were first captured while the patient was in the 25° back-up position and then while the patient was in the flat supine position. An anaesthetist blinded to the position graded the quality of the images using the percentage of glottic opening (POGO) score.
Results: Comparing the two positions, mean (SD) POGO scores increased significantly from 42.2 (27.4)% in supine position to 66.8 (27.6)% in 25° back-up position (P < 0.0001).
Conclusions: During laryngoscopy, the laryngeal view, as assessed by POGO scores, improves significantly in the 25° back-up position when compared with the flat supine position.

CANADIAN JOURNAL OF ANESTHESIA - TOP

No evidence for decreased incidence of aspiration after rapid sequence induction
David T. Neilipovitz, MD FRCPC and Edward T. Crosby, MD FRCPC
Canadian Journal of Anesthesia 54:748-764 (2007)

Purpose: The purpose of this structured, evidence-based, clinical update was to determine if rapid sequence induction is a safe or effective technique to decrease the risk of aspiration or other complications of airway management.
Source: In June 2006 a structured search of MEDLINE from 1966 to present using OVID software was undertaken with the assistance of a reference librarian. Medical subject headings and text words describing rapid sequence induction or intubation (RSI), crash induction or intubation, cricoid pressure and emergency airway intubation were employed. OVID’s therapy (sensitivity) algorithm was used to maximize the detection of randomized trials while excluding non-randomized research. The bibliographies of eligible publications were hand-searched to identify trials not identified in the electronic search.
Principal findings: A total of 184 clinical trials were identified of which 163 were randomized controlled trials (RCTs). Of these clinical trials, 126 evaluated different drug regimens with 114 being RCTs. Only 21 clinical trials evaluated non-pharmacologic aspects of the RSI with 18 RCTs identified. A parallel search found 52 trials evaluating cricoid pressure (outside of the context of an RSI technique) with 44 classified as RCTs. Definitive outcomes such as prevention of aspiration and mortality benefit could not be evaluated from the trials. Likewise, the impact on adverse outcomes of the different components of RSI could not be ascertained.
Conclusion: An absence of evidence from RCTs suggests that the decision to use RSI during management can neither be supported nor discouraged on the basis of quality evidence.

PUB MED - TOP

Intravenous conscious sedation in children for outpatient dentistry.
Mikhael MS, Wray S, Robb ND.
Br Dent J. 2007 Sep 22;203(6):323-31

Barking, Havering and Redbridge Hospitals Associate University NHS Trust. magdimikhael@btinternet.com

The use of general anaesthesia for dental treatment in the NHS outside hospitals has changed over time. Although deaths are uncommon during or immediately after general anaesthesia for dental treatment, they are more likely to occur than with other methods of pain and anxiety reduction, such as local anaesthesia and conscious sedation. Inquiries into recent anaesthetic deaths in dental practice have been critical of the standard of care provided in areas such as pre-operative assessment, monitoring, resuscitation and transfer to specialist critical care facilities.

Single use of fentanyl in colonoscopy is safe and effective and significantly shortens recovery time.
Lazaraki G, Kountouras J, Metallidis S, Dokas S, Bakaloudis T, Chatzopoulos D, Gavalas E, Zavos C.
Surg Endosc. 2007 Sep;21(9):1631-6. Epub 2007 Feb 16.

Department of Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece. lazarakg@yahoo.com

BACKGROUND: Colonoscopy remains an uncomfortable examination and many patients prefer to be sedated. The aim of this study was to evaluate the efficacy and safety of intravenous administration of fentanyl in titrated doses compared with intravenous administration of the well-known midazolam in titrated doses. METHODS: One hundred twenty-six patients scheduled for ambulatory colonoscopy were randomly assigned to receive either 25 mcg fentanyl (Fentanyl group, n = 66, 35 females, mean age = 61.5 years) and titrated up to 50 mcg or 2 mg midazolam (Midazolam group, n = 60, 33 females, mean age = 63.2 years) and titrated up to 5 mg. Patients graded discomfort on a scale from 0 to 4 and pain on a scale from 0 to 10. Success of the procedure, time to cecum, complications, and recovery time for each patient were independently recorded. RESULTS: Mean discomfort scores were 0.4 in the Fentanyl group and 1.0 in the Midazolam group (p = 0.002). Similarly, mean scores for pain and anus to cecum time were lower in the Fentanyl group than in the Midazolam group [2.59 vs. 4.43 (p = 0.002) and 8.7 vs. 12.9 min (p = 0.012), respectively]. No adverse events were reported in the Fentanyl group, while in the Midazolam group a decrease in oxygen saturation was noted in 23/60 (35%) patients. Mean recovery time was 5.6 min in the Fentanyl group and 16 min in the Midazolam group (p = 0.014). Mean dosage was 36 mcg for fentanyl and 4.6 mg for midazolam. CONCLUSION: Administration of fentanyl in low incremental doses is sufficient to achieve a satisfactory level of comfort during colonoscopy.

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