Safety and efficacy of extended-release bupivacaine local anaesthetic in open hernia repair: a randomized controlled trial.

BACKGROUND: Pain relief remains a major problem in hernia surgery. SABER-Bupivacaine is an investigational extended-release formulation of bupivacaine in a resorbable matrix, which may provide up to 72 h of local pain relief. METHODS: A double-blinded, randomized controlled trial was undertaken to evaluate the safety and efficacy of SABER-Bupivacaine. Consented patients (n = 124) undergoing open inguinal hernia repair at five sites in Australia and New Zealand were randomized to receive either 2.5 (330 mg) or 5.0 mL (660 mg) of SABER-Bupivacaine or SABER-Placebo administered to the surgical wound at the end of the procedure. Analgesic efficacy and safety was evaluated. RESULTS: SABER-Bupivacaine appeared safe with no difference in the incidence of side effects compared with SABER-Placebo. The 5.0 mL dose of SABER-Bupivacaine reduced the mean area under the curve of pain intensity on movement compared with SABER-Placebo (2.47 versus 3.60; P = 0.0033) and decreased the number of patients requiring supplemental opioids by 26% (although not statistically significant; P = 0.0909). Normal wound healing was reported throughout the trial and at 3- and 6-month follow-up in every treatment group. CONCLUSION: After open inguinal hernia repair, SABER-Bupivacaine administered at the surgical site was safe and provided pain relief, reduced the need for supplemental (oral and parenteral) analgesia and did not impair wound healing.

Targeting oxidative stress in surgery: effects of ageing and therapy.

In the current era cardiac surgeons are being called upon to operate upon older, sicker patients. The effect is to augment oxidative stress and increase the rate of post-operative complications and ultimately mortality. We have developed antioxidant-based pre-treatment regimes initially based on coenzyme Q(10). A randomised trial of coenzyme Q(10) in elective cardiac surgery patients demonstrated augmented plasma and cardiac mitochondrial membrane coenzyme Q(10) content, improved mitochondrial respiration and increased myocardial tolerance of oxidative stress. The addition of omega-3 polyunsaturated fatty acids, alpha-lipoic acid, selenium and magnesium orotate in a second clinical trial, improved post-operative recovery with demonstrable reductions in myocardial damage, rate of atrial fibrillation and length of hospital stay. Finally we performed a pilot study of this combined metabolic therapy regimen to which we added preoperative physical exercise and mental stress reduction with indications of further improvements in post-operative recovery. We conclude that simultaneously targeting a number of key deficiencies with a metabolic formulation prior to surgery results in peri- and post-operative clinical and economic benefits.

The clinical application of metabolic therapy for cardiovascular disease.

Metabolic therapy involves the administration of a substance normally found in the body to enhance a metabolic reaction within the cell. This may be achieved in two ways. Firstly, for some systems a substance can be given to achieve greater than normal levels in the body so as to drive an enzymic reaction in a preferred direction. Secondly, metabolic therapy may be used to correct an absolute or relative deficiency of a cellular component. Thus, metabolic therapy differs greatly from most standard cardiovascular pharmacologic therapies such as the use of ACE Inhibitors, beta-blockers, statins and calcium channel antagonists that are given to block rather than enhance cellular processes.

Pre-operative preparation for cardiac surgery utilising a combination of metabolic, physical and mental therapy.

UNLABELLED: Cardiac surgery represents major metabolic, physical and mental stresses associated with an increased production of reactive oxygen species. These stresses may hamper post-operative recovery, increasing hospitalisation times and operative mortality. We conducted a quality assurance and feasibility study to evaluate and monitor the safety and efficacy of a new program of combined pre-operative metabolic (enhanced antioxidant), physical and mental therapy to counter these stresses prior to cardiac surgery. METHODS: Sixteen cardiac surgery patients received metabolic therapy consisting of the antioxidants coenzyme Q(10) (CoQ(10)) (300 mg) and alpha-lipoic acid (300 mg), combined with magnesium orotate (1200 mg), and omega-3 fatty acids (3g) given daily for a mean 36+/-7 days up until the day of operation. Patients also received a regimen of physical therapy incorporating non-exhaustive, light exercise and stretching techniques. Mental therapy in the form of stress reduction, relaxation and music was also provided. Blood levels of CoQ(10) and malondialdehyde (MDA) were measured and a quality of life (QoL) questionnaire (SF-36) was administered before, after the program and 1 month after surgery. A patient satisfaction survey was conducted at six weeks post-operatively. RESULTS: During the pre-operative period, treated patients (n=16) showed significant improvements in QoL composite scores, physical (33.5+/-4.1 to 41.0+/-4.5, p=0.005) and mental (44.3+/-4.5 to 54.1+/-5.3, p=0.006). CoQ(10) levels increased from 725.6+/-96.1 nmol/l to 3019.9+/-546.4 nmol/l (p=0.006), MDA levels decreased from 2.2+/-0.9 microM to 1.4+/-0.7 microM (p=0.013) and systolic blood pressure decreased from 140+/-4.0 mmHg to 132+/-3.0 mmHg (p=0.002). One month after surgery the treated group (n=14) demonstrated significant improvements from pre-operative baseline in QoL composite scores, physical (38.9+/-4.0 to 57.9+/-5.4, p=0.01) and mental (50.3+/-5.6 to 69.3+/-4.8, p=0.03) compared to a previously reported similar group of cardiac surgery patients (n=74) whose physical and mental scores decreased from 43.0 to 42.8 (p=0.05) and 53.8 to 49.8, respectively (p=0.05). CONCLUSION: These preliminary results suggest that a program of combined metabolic, physical and mental preparation before cardiac surgery is safe, feasible and may improve quality of life, lower systolic blood pressure, reduce levels of oxidative stress and thus has the potential to enhance post-operative recovery.

Cardiac surgery in octogenarians.

BACKGROUND: Early and late results were studied in order to improve the indications for surgery in the elderly. METHODS: Two hundred and thirty-seven patients aged 80 years or older underwent cardiac surgery between 1987 and 2001. The mean age of patients, which included 148 men and 89 women, was 82 years. Elective operations were performed in 194 patients and urgent or emergency operations in 43. Coronary artery bypass grafting (CABG) was performed in 104 patients, valve surgery in 60, CABG plus valve in 58, and other surgery in 15. Late results were obtained in 91% of patients, and the mean follow-up period was 54 months. RESULTS: Operative mortality was 9% in total; 7% in CABG, 5% in valve, 10% in CABG plus valve. Operative mortality was significantly higher in the urgent/emergency group than in the elective group (25% vs 6%). The actuarial survival rate for hospital survivors at 60 months after surgery was 75% and the mean survival period 76 months. There were no significant differences among operations. Preoperatively 81% of the patients had been in New York Heart Association class III or IV, and 88% of survivors were in class I or II in the late period. CONCLUSIONS: Early and late results for elective surgery in octogenarians are satisfactory. However, for urgent or emergent cases, there is a marked increase in morbidity and mortality.

Response of the senescent heart to stress: clinical therapeutic strategies and quest for mitochondrial predictors of biological age.

The aging heart has an impaired response to many kinds of stress. In clinical practice, there is a need for senescence-specific therapies to protect against stress and for biochemical markers of senescence to identify those patients most in need of therapy. In isolated rat hearts, in human tissues, and in a clinical trial, we have shown previously that coenzyme Q(10) has the ability to protect the heart against stress especially in senescence. We recently have devised a regimen of therapy to protect the senescent heart against stress, combining metabolic therapy (coenzyme Q(10), alpha lipoic acid, magnesium orotate, and omega 3 polyunsaturated fatty acids) with physical exercise and mental stress reduction. The preliminary results of this program are promising. In an endeavor to predict the likely response of individual senescent hearts to stress, we correlated the tissue load of mitochondrial DNA deletions and total cellular mitochondrial DNA copy number in human cardiac tissue with recovery of the same tissue from ischemia/reperfusion stress. We found that these mitochondrial markers actually were less predictive of impaired response to stress than age alone. We conclude that the aging heart has a diminished capacity to recover from stress that is not readily predictable by cardiac content of intact mitochondrial DNA and that this recovery can be improved by metabolic therapy combined with physical exercise and mental stress reduction.

The principles of metabolic therapy for heart disease.

Metabolic therapy involves the administration of a substance normally found in the body to enhance a metabolic reaction within the cell. This may be achieved in two ways. First, for some systems, a substance can be given to achieve greater than normal levels in the body so as to drive an enzymic reaction in a preferred direction. Second, metabolic therapy may be used to correct an absolute or relative deficiency of a cellular component. Thus, metabolic therapy differs greatly from most standard cardiovascular pharmacologic therapy such as the use of ACE Inhibitors b-blockers, statins and calcium channel antagonists that are given to block rather than enhance cellular processes. In this review we highlight some metabolic substances that have potential benefit in treating heart disease or improving outcomes after cardiovascular interventions. Glucose-insulin-potassium therapy is protective against myocardial ischaemia by elevating myocardial glycogen levels. Coenzyme Q(10) is a lipid-soluble antioxidant that plays a crucial role in cellular ATP production. Magnesium orotate, a key intermediate in the biosynthetic pathway of glycogen, has been shown to improve the energy status of the cell and improve recovery from cardioplegic arrest. The amino acid aspartate plays an important role in providing energy substrates for oxidative phosphorylation in the myocyte. By improving cellular energy production, metabolic therapy has the potential to benefit cardiac function during the stress of cardiac surgery, myocardial infarction and cardiac failure.