Background At therapeutic concentrations, cytochrome P4502B6 (CYP2B6) is the major P450 isoform catalyzing hepatic ketamine N-demethylation to norketamine in vitro. The CYP2B6 gene is highly polymorphic. The most common variant allele, CYP2B6*6, is associated with diminished hepatic CYP2B6 expression and catalytic activity compared with wild-type CYP2B6*1/*1. CYP2B6.6, the protein encoded by the CYP2B6*6 allele, and liver microsomes from CYP2B6*6 carriers had diminished ketamine metabolism in vitro. This investigation tested whether humans with the CYP2B6*6 allele would have decreased clinical ketamine metabolism and clearance. Methods Thirty volunteers with CYP2B6*1/*1, *1/*6, or *6/*6 genotypes (n = 10 each) received a subsedating dose of oral ketamine. Plasma and urine concentrations of ketamine and the major CYP2B6-dependent metabolites were determined by mass spectrometry. Subjects’ self-assessment of ketamine effects were also recorded. The primary outcome was ketamine N-demethylation, measured as the plasma norketamine/ketamine area under the curve ratio. Secondary outcomes included plasma ketamine enantiomer and metabolite area under the plasma concentration–time curve, maximum concentrations, apparent oral clearance, and metabolite formation clearances. Results There was no significant difference between CYP2B6 genotypes in ketamine metabolism or any of the secondary outcome measures. Subjective self-assessment did reveal some differences in energy and level of awareness among subjects. Conclusions These results show that while the CYP2B6*6 polymorphism results in diminished ketamine metabolism in vitro, this allelic variant did not affect single, low-dose ketamine metabolism, clearance, and pharmacokinetics in vivo. While in vitro drug metabolism studies may be informative, clinical investigations in general are needed to validate in vitro observations.

Background. Patients with head and neck cancer often have multiple risk factors for coronary artery disease. Yet, little is known about the incidence of postoperative myocardial injury after major head and neck cancer surgery and its clinical relevance. The aim of this study was to determine the risk of postoperative myocardial injury in patients undergoing major head and neck cancer surgery.Methods. This was a retrospective cohort study of all patients who underwent major head and neck cancer surgery (n ¼ 378) at a single major academic center from April 2003 to July 2008. Peak postoperative troponin I (TnI) concentration was the primary outcome.Results. Of 378 patients who underwent major head and neck cancer surgery, 57 patients (15%) had development of an elevated TnI; 90% of these occurred within the first 24 hours after surgery. Preexisting renal insufficiency (unadjusted OR [OR]: 4.60; 95% CI 1.53-13.82), coronary artery disease (OR: 2.33; 95% CI 1.21-4.50), peripheral vascular disease (OR: 2.83; 95% CI 1.31-6.14), hypertension (OR: 2.22; 95% CI 1.20-4.12), and previous combined chemotherapy and radiation (OR: 2.68; 95% CI 1.04-6.91) were associated with elevated postoperative TnI levels. Patients with elevated TnI levels had a significantly longer length of stay in the hospital (8.5 vs 10.1 days; p ¼ .014) and ICU (3 vs 4.5 days; p ¼ .001) and an 8-fold increased risk of death at 60 days after surgery (adjusted OR: 8.01, 95% CI 2.03-31.56). At 1 year, patients with an abnormal postoperative TnI level were twice as likely to die (OR 1.93; 95% CI 1.02-3.63).Conclusions. Patients who undergo major head and neck cancer surgery are at significant risk for postoperative myocardial injury, which is a strong predictor of 60-day mortality after surgery. Monitoring of myocardial injury during the first postoperative days, as well as optimizing preventive cardiac care, may be helpful to reduce postoperative mortality rates. Head Neck 33: 1085-1091, 2011Keywords: Myocardial infarction; Outcomes; Troponin Worldwide more than half a million new cases of head and neck cancer are diagnosed each year.1 Head and neck cancer is commonly caused by long-term tobacco and alcohol abuse.2 Long-term smoking and tobacco abuse increases the risk for not only cancer but also coronary artery disease and myocardial infarction. Most patients present with advanced-stage cancer, and many will undergo treatment with surgery either as the initial therapy or as salvage surgery after previously failed radiotherapy or chemoradiotherapy.Surgery for head and neck cancer is complex and extensive because it commonly involves the resection of the tumor and unilateral or bilateral radical neck dissection and often requires transfer of a tissue flap for reconstruction.1 Major head and neck cancer surgery frequently lasts more than 8 hours, involves large fluid shifts and blood loss, and causes significant postoperative inflammation and pain. All these factors are considered important risk factors for postoperative myocardial injury.Postope...

Supplemental Digital Content is Available in the Text. Baseline mechanical pain threshold does not predict analgesic response to pregabalin in painful chemotherapy-induced peripheral neuropathy caused by docetaxel, paclitaxel, or oxaliplatin.

Background Head and neck cancer patients often have multiple risk factors for coronary artery disease. Yet, little is known about the incidence of postoperative myocardial injury after major head and neck cancer surgery and its clinical relevance. The aim of the study was to determine the risk of postoperative myocardial injury in patients undergoing major head and neck cancer surgery. Methods Retrospective cohort study of all patients who underwent major head and neck cancer surgery (n=378) at a single major academic center from April 2003 to July 2008. Peak postoperative troponin I (TnI) concentration was the primary outcome. Results Of 378 patients, who underwent major head and neck cancer surgery, 57 patients (15%) developed an elevated TnI; 90% of which occurred within the first 24 hours after surgery. Pre-existing renal insufficiency (unadjusted OR [OR]: 4.60, 95% CI 1.53–13.82), coronary artery disease (OR: 2.33, 95% CI 1.21–4.50), peripheral vascular disease (OR: 2.83, 95%CI 1.31–6.14), hypertension (OR: 2.22, 95% CI 1.20–4.12), and previous combined chemotherapy and radiation (OR: 2.68, 95% CI 1.04–6.91) were associated with elevated postoperative TnI. Patients with elevated TnI had a significantly longer length of stay in the hospital (8.5 vs. 10.1 days; p= 0.014) and ICU (3 vs. 4.5 days; p= 0.001) and an 8-fold increased risk of death at 60 days after surgery (adjusted OR: 8.01, 95% CI 2.03 – 31.56). At one year, patients with an abnormal postoperative TnI were twice as likely to die (OR 1.93; 95% CI 1.02 – 3.63). Conclusions Patients who undergo major head and neck cancer surgery are at significant risk for postoperative myocardial injury which is a strong predictor of 60-day mortality after surgery. Monitoring of myocardial injury during the first postoperative days as well as optimizing preventive cardiac care may be helpful to reduce postoperative mortality.

Summary Nitrous oxide inactivates vitamin B12 with detrimental consequences for folate and methionine metabolism. This inactivation can be clinically detected by an increase in plasma total homocysteine. In a clinical trial, we tested the hypothesis that a preoperative infusion of vitamin B12 and folate prevents the nitrous oxide-induced homocysteine increase. Sixty-three healthy patients scheduled for elective surgery were randomly allocated to receive (a) B-vitamins and nitrous oxide; (b) placebo and nitrous oxide or (c) normal saline and no nitrous oxide. Fifty-nine patients were included in the final study population. After intravenous B-vitamin infusion, plasma vitamin B12 and folate concentrations increased 35-fold and 12-fold on the first postoperative measurement, respectively. Patients who received B-vitamins developed a similar increase (+18%) in homocysteine after nitrous oxide (+ 1.9 μmol.L−1; 95% CI: 0.2 – 3.6 μmol.L−1) as patients who did not receive B-vitamins (+ 22%; + 2.7 μmol/L; 95% CI: 0.6 – 4.8 μmol.L−1). Patients who did not receive nitrous oxide (“air control”) had no change in homocysteine (+ 0.5 μmol.L−1; 95% CI: −0.8 – 1.9 μmol.L−1). This trial indicates that preoperative IV B-vitamins may not prevent nitrous oxide-induced hyperhomocysteinemia.

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Registration for this trial along with the study protocol can be found at clinicaltrials.gov (NCT02363803). S.H. had full access to all data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis; he is the Guarantor.

Severe, uncontrolled pain remains common in populations with serious or life-threatening illness. Despite the availability of oral opioid therapy in most developed countries, over 50% of persons with advanced, metastatic, or terminal cancer continue to have moderate to severe pain. Published guidelines endorse the view that these patients should be considered for procedural, or so-called interventional, pain therapies. Generally accepted indications for interventional pain therapies include (a) uncontrolled pain despite systemic analgesics and (b) unacceptable systemic analgesic adverse effects. This chapter describes these therapies and discusses how they are best used within a multimodal strategy for symptom management. Interventional pain therapies are now incorporated into best practices for cancer pain management. These therapies, especially spinal analgesics, neurolytic coeliac plexus block, and vertebroplasty, have become essential components of palliative care, in order to control pain that cannot be safely and effectively managed with systemic analgesics.