The transition from acute to chronic post surgical pain.

All chronic pain was once acute, but not all acute pain becomes chronic. The transition of acute postoperative pain to chronic post surgical pain is a complex and poorly understood developmental process. The manuscript describes the various factors associated with the transition from acute to chronic pain. The preoperative, intraoperative and postoperative surgical, psychosocial, socio-environmental and patient-related factors and the mechanisms involved are discussed and preventive (or limitation) strategies are suggested. In future, the increasing understanding of genetic factors and the transitional mechanisms involved may reveal important clues to predict which patients will go on to develop chronic pain. This may assist the development of appropriate interventions affecting not only the individual concerned, but also ultimately the community at large.

In-hospital cardiac arrest: different wards show different survival patterns.

The purpose of the study was to investigate the characteristics and outcomes of in-hospital cardiac arrests that occurred outside of the hospital critical care areas. A prospective register of adult in-hospital cardiac arrests occurring in non-critical care areas of Christchurch Hospital, Christchurch, New Zealand, from January 2001 to December 2004 was compiled. Two-hundred-and-forty-three cardiac arrests were recorded in this period. The overall return of spontaneous circulation was 38.7% (CI 32.6, 44.8) and survival to discharge was 21.0% (CI 15.9, 26.1). Comparison of clinical areas showed that the percentage with successful resuscitation and the percentage with survival to discharge were highest in the cardiology wards (52.2%, 41.3%) and lowest in the medical wards (24.9%, 8.8%). After taking account of rhythm, age, gender and time of day, differences between clinical areas were slightly reduced. Cardiology wards, however, still had a higher resuscitation percentage than medical wards (P = 0.03) and a higher percentage with survival to discharge than all other areas (P = 0.005 overall, P < or = 0.05 for each individual comparison). Reporting of hospital-wide survival rates does not accurately reflect the survival rates in a variety of specific clinical areas. The analysis of outcomes across different clinical areas at Christchurch Hospital revealed differences in outcomes and therefore the clinical experience of staff in those areas. These differences have implications for the resuscitation training of health professionals. The further development of national resuscitation registries may allow more specific analysis of outcomes in different clinical areas.

Flagging the pain: preventing the burden of chronic pain by identifying and treating risk factors in acute pain.

Chronic pain represents a major public health problem that impacts negatively on quality-of-life issues and healthcare costs. Unrelieved acute post-traumatic and postoperative pains are risk factors in the development of chronic pain, although psychological and environmental factors are at work as well. Flagging pain (blue, yellow and red flags) helps to identify risk factors in acute pain that need attention to avoid the transition from acute postoperative pain to acute persistent and then on to chronic pain. This offers a unique opportunity for preventative medicine.

Mitochondrial myopathies and anaesthesia.

The mitochondrial myopathies consist of a heterogeneous group of disorders caused by structural and functional abnormalities in mitochondria leading to involvement of the nervous system and muscles as well as other organ systems. The peculiar genetic characteristics of mitochondrial DNA impart distinctive properties to these disorders. The pathophysiology is presented. The methods employed in making the correct diagnosis, the preoperative patient assessment and correction of metabolic dysfunctions and anaesthetic techniques used, are highlighted. The conditions are briefly reviewed and suggestions are made for the safe anaesthetic management of affected patients.

Intranasal sufentanil/midazolam versus ketamine/midazolam for analgesia/sedation in the pediatric population prior to undergoing multiple dental extractions under general anesthesia: a prospective, double-blind, randomized comparison.

This article details a double-blind, randomized study evaluating the efficacy and safety of intranasal sufentanil and intranasal midazolam (S/M) when compared with intranasal ketamine and intranasal midazolam (K/M) for sedation and analgesia in pediatric patients undergoing dental surgery. Fifty healthy ASA status 1 children aged 5-7 years, weighing 15-20 kg, and having 6 or more teeth extracted, were randomly allocated to 2 groups of 25 patients each (n = 50). In the S/M group, 25 children received intranasal sufentanil 20 microg, and intranasal midazolam 0.3 mg/kg 20 minutes before the induction of anesthesia. In the K/M group, 25 children received intranasal ketamine 5 mg/kg and intranasal midazolam 0.3 mg/kg 20 minutes before the induction of anesthesia. Sevoflurane in nitrous oxide and oxygen was used for induction and maintenance of anesthesia. This study demonstrated the safety and efficacy of both methods with ease of administration, combined with a rapid onset of action. Both groups were equally sedated. A smooth mask induction of anesthesia was experienced in the majority of children. Effective postoperative analgesia for multiple dental extractions was provided. The intranasal administration of drugs for sedation and analgesia has some promising features in preschool children undergoing multiple dental extractions.

An evaluation of analgesic efficacy and clinical acceptability of intravenous tramadol as an adjunct to propofol sedation for third molar surgery.

This article details a double-blind, randomized, placebo-controlled pilot study evaluating the analgesic efficacy and clinical acceptability of intravenous tramadol in patients undergoing surgical removal of an impacted third molar tooth under local anesthesia and intravenous sedation with propofol. Forty-five ASA status 1 dental outpatients were randomly allocated to 2 groups of 22 (group A) and 23 (group B) patients each (n = 45). Group A (T/P) received intravenous tramadol 1.5 mg/kg injected over 2 minutes, followed by a bolus dose of intravenous propofol 0.4 mg/ kg. Maintenance consisted of a continuous infusion of propofol 3 mg/kg/h, with an additional bolus dose of 0.4 mg/kg intravenously 2-3 minutes prior to the infiltration of the local anesthetic solution. Group B (P/P) patients received no tramadol but instead a saline placebo solution and an identical amount of propofol. Overall, in this study, postoperative pain was much better controlled in the group receiving tramadol 1.5 mg/kg intravenously despite there being no significant difference in the dose of propofol administered in both groups. Intravenous tramadol, when given with propofol, did not affect the cardiovascular, respiratory, and sedative effects of propofol. Following tramadol, despite being an opioid, no nausea and vomiting were reported in the early postoperative period, indicating the value of using tramadol with propofol. Thus, this pilot study demonstrated the potential use of intravenous tramadol with propofol in day-case dento-alveolar surgery.

Tramadol--a multimodal, multipurpose analgesic for the surgeon.

Tramadol is a multimodal analgesic with proven dose-related efficacy over a variety of perioperative surgical fields and is efficacious in treating both neuropathic and cancer pain. It is of particular use in patients with impaired cardiorespiratory, hepatic or renal function, and is an important addition to the armamentarium of the surgeon.

Pharmacokinetics of oral tramadol drops for postoperative pain relief in children aged 4 to 7 years--a pilot study.

Tramadol hydrochloride is an analgesic with mu receptor activity suitable for administration to children as oral drops. As the serum concentration profile and pharmacokinetic parameters in young children are not known via this route, we studied 24 healthy ASA 1 children to determine those parameters. The children's mean age was 5.3 +/- 1.1 years and their mean weight was 17.8 +/- 3.1 kg. They underwent general anesthesia with sevoflurane for dental surgery. The mean duration of anesthesia was 27.9 +/- 10.1 minutes. Tramadol 1.5 mg/kg (this dose was chosen because we have previously shown it to be effective in providing analgesia following pediatric dental surgery) was administered as oral drops 30 minutes before anesthesia. Venous blood samples were taken following the tramadol at 30-minute intervals for 4 hours, every 2 hours for 6 hours, and every 4 hours for 12 hours. The samples were centrifuged and the serum stored at -20 degrees C, and nonstereoselective gas chromatography was used to determine the concentration of (+) and (-) tramadol enantiomers plus their o-demethyltramadol (M1) metabolite concentrations. The tramadol absorption was rapid, the maximum measured serum concentration present occurring before the first sample at 30 minutes. That first sample had a concentration of 352 +/- 83.4 ng/mL. The concentration remained above the 100 ng/mL analgesic level until 6.8 +/- 0.9 hours. The elimination half-life was 3.6 +/- 1.1 hours, the serum clearance 5.6 +/- 2.7 mL/kg/min, and the volume of distribution 4.1 +/- 1.2 L/kg. The (+) enantiomer concentration was 14.2 +/- 4.9% greater than that of the (-) enantiomer. The M1 metabolites had a (-) enantiomer concentration 92.3 +/- 75.1% greater than the (+) enantiomer. From the peak concentration at 4.5 +/- 1.5 hours, the concentration of the metabolite was approximately one third that of the parent drug. The M1 elimination half-life was 5.8 +/- 1.7 hours. Apart from the rapid rise in the serum concentration, these kinetic parameters are similar to those seen in healthy young adults. The concentration profile supports an effective clinical duration in the region of 7 hours.

Long QT syndrome and anaesthesia.

The long QT syndrome is a disorder of myocardial electrical conduction that leaves the heart vulnerable to the ventricular tachydysrhythmia torsade de pointes. Clinically, this results in syncope or sudden death. The long QT syndrome may be congenital, if caused by abnormal myocardial potassium or sodium ion channels, or acquired, if due to drugs, electrolyte abnormalities or metabolic conditions. Triggers for the development of torsade de pointes include both anaesthesia and surgery. Some anaesthetic agents prolong the QT interval. The condition is reviewed and suggestions are made for the anaesthetic management of affected patients.

Tramadol--present and future.

The atypical opioid, tramadol, has recently been introduced into Australia and New Zealand. Tramadol's efficacy in a wide range of acute and chronic pain states, its multi-formulation availability, and its low serious side-effect potential at high doses and in prolonged therapy, combine to bestow on it a user-friendly profile, for short- and long-term use in hospitals and communities. This paper reviews the following: its formulation and routes of administration; its unique enantiomeric biochemistry and metabolism; its triple mechanisms of action; its pharmacokinetics and pharmacodynamics; its analgesic efficacy compared with other opioids; the indications for its clinical use in a variety of acute and chronic (including cancer) painful states; its specific use in the elderly, in paediatric and in obstetric patients; its adverse event (including drug interaction) and safety profile; its advantages in terms of its relative lack of respiratory depression, major organ toxicity and histamine release, and dependence and abuse potential. The review looks at new uses for this drug and what can be expected in this area in the future.

Beneficial effects of weight loss associated with moderate calorie/carbohydrate restriction, and increased proportional intake of protein and unsaturated fat on serum urate and lipoprotein levels in gout: a pilot study.

OBJECTIVES: Insulin resistance (IR) has been increasingly implicated in the pathogenesis of gout. The lipoprotein abnormalities described in hyperuricaemic subjects are similar to those associated with IR, and insulin influences renal urate excretion. In this study it was investigated whether dietary measures, reported to be beneficial in IR, have serum uric acid (SU) and lipid lowering effects in gout. METHODS: Thirteen non-diabetic men (median age 50, range 38-62) were enrolled. Each patient had had at least two gouty attacks during the four months before enrollment. Dietary recommendations consisted of calorie restriction to 6690 kJ (1600 kcal) a day with 40% derived from carbohydrate, 30% from protein, and 30% from fat; replacement of refined carbohydrates with complex ones and saturated fats with mono- and polyunsaturated ones. At onset and after 16 weeks, fasting blood samples were taken for determination of SU, serum cholesterol (C), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglycerides (TGs). Results were expressed as median (SD). RESULTS: At onset, the body mass index (BMI) was 30.5 (8.1) kg/m(2). Dietary measures resulted in weight loss of 7.7 (5.4) kg (p=0.002) and a decrease in the frequency of monthly attacks from 2.1 (0.8) to 0.6 (0.7) (p=0.002). The SU decreased from 0.57 (0.10) to 0.47 (0.09) mmol/l (p=0.001) and normalised in 7 (58%) of the 12 patients with an initially raised level. Serum cholesterol decreased from 6.0 (1.7) to 4.7 (0. 9) mmol/l (p=0.002), LDL-C from 3.5 (1.2) to 2.7 (0.8) mmol/l (p=0. 004), TGs from 4.7 (4.2) to 1.9 (1.0) mmol/l (p=0.001), and C:HDL-C ratios from 6.7 (1.7) to 5.2 (1.0) (p=0.002). HDL-C levels increased insignificantly. High baseline SU, frequency of attacks, total cholesterol, LDL-C and TG levels, and total C:HDL-C ratios correlated with higher decreases in the respective variables upon dietary intervention (p<0.05). CONCLUSION: The results suggest that weight reduction associated with a change in proportional macronutrient intake, as recently recommended in IR, is beneficial, reducing the SU levels and dyslipidaemia in gout. Current dietary recommendations for gout may need re-evaluation.

Hyposecretion of adrenal androgens and the relation of serum adrenal steroids, serotonin and insulin-like growth factor-1 to clinical features in women with fibromyalgia.

Neuroendocrine deficiencies have been implicated in fibromyalgia (FM). In the present study, adrenal androgen metabolites and their relationship with health status in FM were investigated. For comparison, serum levels of other implicated neuroendocrine mediators were correlated with health status. Fifty-seven consecutive women with FM completed the Fibromyalgia Impact Questionnaire (FIQ). Fasting blood samples were taken for measurement of dehydroepiandrosterone sulphate (DHEAS), free testosterone (T), cortisol, serotonin and insulin-like growth factor-1. Normal value for DHEAS and T were obtained from 114 controls. DHEAS levels were decreased significantly in pre- and postmenopausal patients (P<0.0001 and P<0.0005, respectively). T levels were decreased significantly in premenopausal and insignificantly in postmenopausal patients (P<0.0001 and P=0.06, respectively). The following correlations between neurohormonal levels and FIQ scores were found: DHEAS (after adjustment for age) vs. pain (P<0.001) and T (after adjustment for age) versus physical functioning (P=0.002). None of the other neurohormonal levels correlated significantly with any of the FIQ scores. IGF-1 levels were lower in the obese patients as compared to those who were non-obese (P=0.03). The BMI correlated positively with pain (P<0. 001) and inversely with DHEAS levels (P=0.006). After further adjustment for BMI, the correlation between age adjusted DHEAS and pain was no longer significant. Hyposecretion of adrenal androgens was documented in FM. This was more pronounced in obese patients. Low serum androgen levels correlated with poor health status in FM. Longitudinal studies are needed to elucidate whether these are cause and/or effect relationships.

Re-evaluation of i.m. ephedrine as prophylaxis against hypotension associated with spinal anaesthesia for Caesarean section.

PURPOSE: To assess the safety and efficacy of 37.5 mg ephedrine i.m. in preventing hypotension associated with spinal anaesthesia for Caesarean section. METHODS: In a double-blind randomised controlled study, 40 patients (20 in each group) were given either 37.5 mg ephedrine or placebo i.m. The following parameters were recorded: (i) blood pressure; (ii) heart rate; (iii) ephedrine i.v. supplementation; (iv) umbilical venous blood gases and neonatal Apgar scores. RESULTS: The incidence of hypertension in the study group was 30% compared with 20% for the control group (P:NS). There was no difference in mean highest blood pressure or mean highest heart rate between the groups. The incidence of hypotension was lower but not significantly lower in the study group (50%) than in the control group (80%) (P:NS). However, the incidence of delayed hypotension was only 10% in the study group patients compared with 50% in the control group patients (P < 0.05). CONCLUSION: Giving 37.5 mg ephedrine i.m. prior to spinal anaesthesia was not associated with reactive hypertension or tachycardia. Intramuscular ephedrine provided more sustained cardiovascular support than intravenous ephedrine.

Comparison of tramadol and morphine via subcutaneous PCA following major orthopaedic surgery.

PURPOSE: To compare subcutaneous PCA tramadol with subcutaneous PCA morphine for postoperative pain relief after major orthopaedic surgery and for the incidence of side-effects. METHODS: In a double-blind randomised controlled study 40 patients (20 in each group) self-administered either tramadol or morphine for 72 hr after surgery via s.c. PCA. The following variables were recorded at various time intervals: (i) pain score by means of a visual analogue scale, (ii) drug consumption and total PCA demands, (iii) vital signs (blood pressure and heart rate), (iv) oxygen saturation and respiratory rate, and (v) side-effects (sedation, nausea/vomiting, pruritus, urinary retention and constipation). RESULTS: Both drugs provided effective analgesia. The mean consumption in the first 24 hr was 792 +/- 90 mg tramadol and 42 +/- 4 mg morphine. Thereafter, consumption of both drugs declined markedly. Moderate haemodynamic changes were observed in both the tramadol and morphine groups (with a maximum 20% decrease in mean blood pressure and a maximum 17% increase in heart rate) during the 72 hr period. Both tramadol and morphine were associated with a clinically and statistically significant (P < 0.001) decrease in oxygen saturation, but without changes in respiratory rates. Desaturation was less marked with tramadol. Tramadol appeared to cause more nausea and vomiting than morphine. Sedation was mild and only seen during the first few hours after surgery in both groups. CONCLUSION: Tramadol is an effective analgesic agent for the relief of acute postoperative pain when administered by PCA via the subcutaneous route. Under these conditions tramadol behaves much like morphine with a similar side-effect profile.