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Cancer treatment frequently requires a multimodality approach, involving surgical resection(s), radiotherapy, and chemotherapy. Advanced surgical approaches allow for the combination of two of these, offering patients intraoperative radiotherapy with surgical resection or intraoperative chemotherapy targeted and limited to a particular body region. The systemic toxic effect on nontargeted organs is always a concern in chemotherapy treatment. This potential limitation canminimize the dosage to that less than necessary for killing the intended malignancy. One option for overcoming this problem is administration of chemotherapy in a regionally limited method, which would expose the tumor to high drug concentrations yet reduce systemic exposure. In recent years, the practice of cytoreductive surgery combined with hyperthermic chemotherapy applied regionally has advanced as a treatment for cancermanagement. The incorporation of a hyperthermic variable improves the efficacy of numerous regionally administered chemotherapeutic agents. Malignant cells show a selective sensitivity to hyperthermia, and various causes have been hypothesized. On a cellular level, the tumor cells’ oxidative metabolism is inhibited, resulting in a lower pH and, in turn, an increase in lysosomal activity and cell death. In addition, membrane protein denaturation and an increase in vascular permeability may

Background This study investigated the ability of the modified continual reassessment method (MCRM) to determine the maximum tolerated dose of the opioid antagonist nalmefene, which does not reverse analgesia in an acceptable number of postoperative patients receiving epidural fentanyl in 0.075% bupivacaine. Methods In the postanesthetic care unit, patients received a single intravenous dose of 0.25, 0.50, 0.75, or 1.00 microg/kg nalmefene. Reversal of analgesia was defined as an increase in pain score of two or more integers above baseline on a visual analog scale from 0 through 10 after nalmefene administration. Patients were treated in cohorts of one, starting with the lowest dose. The maximum tolerated dose of nalmefene was defined as that dose, among the four studied, with a final mean probability of reversal of anesthesia (PROA) closest to 0.20 (ie., a 20% chance of causing reversal). The modified continual reassessment method is an iterative Bayesian statistical procedure that, in this study, selected the dose for each successive cohort as that having a mean PROA closest to the preselected target PROA of 0.20. Results The modified continual reassessment method repeatedly updated the PROA of each dose level as successive patients were observed for presence or absence of ROA. After 25 patients, the maximum tolerated dose of nalmefene was selected as 0.50 microg/kg (final mean PROA = 0.18). The 1.00-microg/kg dose was never tried because its projected PROA was far above 0.20. Conclusions The modified continual reassessment method facilitated determination of the maximum tolerated dose ofnalmefene . Operating characteristics of the modified continual reassessment method suggest it may be an effective statistical tool for dose-finding in trials of selected analgesic or anesthetic agents.

Few situations present greater potential for airway management challenges than head and neck oncologic surgery. Such patients often present to the operating room with conditions that make mask ventilation and tracheal intubation potentially or obviously difficult following the induction of general anesthesia. 21 Frequently, the surgical procedures are lengthy, especially those involving plastic reconstruction of a large defect. The surgical team usually requires complete and easy access to the operative site, which is either the airway itself or an area near it. 20 The anesthesiologist may not be able to position him or herself near the patient's head, 30 yet, the surgical team expects the timely establishment of general anesthesia in the patient, a quiet operative field free of bulky equipment, and the patient's smooth emergence from anesthesia at the end of the operation. 20 This article describes a concise and safe approach for securing and managing the airways of patients undergoing surgical therapy for head and neck cancer. The approach is based on current airway management principles and techniques and emphasizes the prevention of airway problems associated with this type of surgery. 58

Postoperative pain can be effectively managed, even in the most complex oncologic procedures. Although the primary agents for treatment of severe pain continue to be opioids, routes of administration and dosing regimen have undergone a dramatic metamorphosis in the past 10 years. The intramuscular injection given every 4 hours has been replaced by patient-controlled analgesia and epidural techniques. Management of ancillary issues that contribute to an increased perception of pain (i.e., stress, depression, anxiety, and inflammation) must be included in an effective multimodal plan. Closer attention to the treatment of pain can obviate the consequences of poorly managed pain, which we are only beginning to understand. In this day of active consumerism in medicine, patients have come to expect improved pain management. Early outcome studies are beginning to confirm the belief that improved pain management translates into between outcomes and earlier dismissals. In the first century BC, Publilius Syrus, a Latin mime, wrote, "There are some remedies worse than the disease." For centuries, pain was inextricably linked to treatment. We may now be approaching a time in the development of medical care when this is no longer true.

Study Objective: To evaluate the safety and efficacy of monitored anesthesia care (MAC) in patients who undergo a novel treatment for hepatocellular cancer in which procedure-related hemodynamic instability is problematic. Design: Nonrandomized open study. Setting: University cancer center operating room. Patients: Nine patients scheduled for hepatic arterial infusion of doxorubicin with complete hepatic venous isolation and extracorporeal chemofiltration (no more than 3 procedures per patient). Interventions: Hepatic venous isolation was achieved with a dual-balloon inferior vena cava catheter connected to an extracorporeal circuit containing chemofilters. Doxorubicin was infused through the hepatic artery and filtered from the venous blood, which was returned to the patient through an internal jugular venous catheter. Each patient received a bolus of propofol (200 μg/kg) and one of alfentanil (2 μg/kg) followed by simultaneous infusions of propofol and alfentanil for percutaneous placement of the catheters and operation of the extracorporeal circuit. Drug rates were varied to maintain a sedative-analgesic state of calm, comfort, minimal movement, and adequate respiratory function. Prior to circuit initiation, patients were preloaded with crystalloid. During circuit operation, hypotension was treated with intravenous (IV) phenylephrine and crystalloid. Measurements and Main Results: End-tidal CO 2 (P ET CO 2 ), respiratory rate, oxygen saturation (SaO 2 ), arterial blood pressure (BP), and heart rate (HR) were monitored. Systolic, diastolic, and mean arterial pressure (MAP), and HR were compared before, during, and after hepatic venous isolation and chemofiltration. Doses and infusion rates of propofol, alfentanil, and phenylephrine were recorded for each treatment. Hypotension occurred in 11 of 13 procedures when blood was directed through the chemofilters and was successfully treated with phenylephrine (dose range 40 to 5,733 μg) and crystalloid. Blood pressure returned to the baseline value on termination of the circuit. Throughout the sedation, patients were easily arousable, analgesia was adequate, and P ET CO 2 level of 38 ± 4 mmHg and SaO 2 greater than 94 % were maintained. Mean doses and infusion rates of MAC drugs were, respectively: propofol, 261 ± 88 mg and 23.7 ± 3.6 μg/kg/min; alfentanil, 3,350 ± 1,468 μg and 0.32 ± 0.14 μg/kg/min. Conclusions: Patients undergoing this novel cancer treatment are safely and effectively managed by MAC achieved with simultaneous infusions of alfentanil and propofol. Procedure-associated hypotension is easily treated with IV phenylephrine and crystalloid.

Background: We performed a phase I study of a novel system of complete hepatic venous isolation and extracorporeal chemofiltration in patients with unresectable hepatocellular carcinoma (HCC) to determine (a) whether systemic exposure to doxorubicin could be limited after high-dose hepatic arterial infusion (HAI), and (b) the hepatic maximum tolerated dose (MTD) of doxorubicin. Methods: Ten patients with biopsy-proven HCC were treated with 20-min HAI of doxorubicin (17 total treatments). Two patients were treated with doxorubicin 60 mg/m2, three patients were treated at 90 mg/m2, and five patients received 120 mg/m2. A newly developed dual-balloon vena cava catheter was advanced from the femoral vein, and the balloons were inflated to isolate and capture total hepatic venous outflow. The hepatic venous blood was pumped through extracorporeal carbon chemofilters before return of the blood to the systemic circulation. Results: Peak systemic doxorubicin levels were an average 85.6% lower than were peak prefilter levels (p

For the patient scheduled for head and neck cancer surgery, careful assessment of the airway demonstrates the most appropriate course of action for securing the airway before surgery begins. Often the patient may be anesthetized safely before intubation of the trachea. The patient may require an awake examination of the airway under sedation and topical analgesia or an awake fiberoptic intubation before the induction of general anesthesia. To secure the airway in some patients, a tracheostomy may be needed. After the operation, extubation of the trachea requires careful attention and may be even more of a challenge than the original intubation. Current principles and techniques for the anesthetic management of the patient undergoing head and neck cancer surgery are reviewed. Emphasis is placed on avoiding the airway problems associated with this kind of surgery.

General anesthesia requires managing a complex array of anesthetic agents that act on an intricate web of neural connections or neural nexus. Both inhaled and intravenous anesthetics must intervene at some level of the neural nexus that provides for amnesia, immobility, hypnosis, and suppression of noxious reflexes. These interactions occur at the spinal and supraspinal level and involve spinal pathways and centers of arousal and memory formation centrally. Current research does not support the notion of a unitary mechanism of action for general anesthetics, but rather that anesthetics act by altering neuronal ion channels and neural communication. In general, anesthetics act by either enhancing inhibitory transmission or blocking excitatory conduction in neural impulses. The potent inhaled agents and most intravenous agents enhance the inhibitory lambda-aminobutyric acid subtype A (GABAA) and glycine channels and depress the excitatory neuronal nicotinic acetylcholine (nnACh) receptors. Nitrous oxide and ketamine act primarily by depressing the excitatory N-methyl-D-aspartate (NMDA) receptors and enhancing the opioid mu receptors. The extent, distribution, and subunit composition of these receptors determine the effects of various anesthetic agents on an individual patient. This variability, both within the patient and among the mechanisms of action of anesthetics, provides a reasonable degree of flexibility to the clinical practice of anesthesia.

The preoperative evaluation and safe anesthetic treatment of patients with endocrine gland tumors mandate an understanding of the physiologic dysfunctions attributable to these tumors. Some patients will exhibit various signs and symptoms characteristic of the MEN syndromes. In the patient with acromegaly, a fiberoptic-guided intubation of the trachea to secure the airway before induction of general anesthesia must be anticipated. Anesthetic treatment of the patient with hyperadrenocorticism requires knowledge of the physiologic effect of excess cortisol. In the patient with severe hyperparathyroidism, we attempt to correct the markedly elevated plasma calcium levels and maintain adequate hydration and urine output perioperatively. Following thyroidectomy for MCT, 2 potential problems of concern are upper airway obstruction and aspiration resulting from injury (unilateral or bilateral) to the recurrent laryngeal nerve and the superior laryngeal nerve, respectively. The major focus during excision of an insulinoma is prevention of wide swings in blood glucose concentrations. In the gastrinoma patient, the anesthesiologist not only must correct any intravascular fluid volume deficit or electrolyte imbalance but must also consider the patient to have a full stomach at the time of anesthetic induction. Correction of hypokalemia and control of hypertension may be required in the preoperative preparation of the patient with an adrenal cortex tumor. Preoperative alpha-adrenergic blockade must be initiated in the patient with a pheochromocytoma to prevent dangerous elevations in blood pressure during anesthesia and surgery for the tumor's removal. Vasodilators with rapid onset and short duration are used to treat intraoperative hypertension. After ligation of the tumor's blood supply, falls in blood pressure may require treatment with fluids and vasopressors. Carcinoid syndrome patients should be treated with somatostatin to prevent stimuli such as anxiety, abdominal scrubbing, or tumor manipulation from precipitating severe hypotension, hypertension, bronchospasm, or tachycardia. In both pheochromocytoma and carcinoid patients, a smooth anesthetic induction and tracheal intubation plus avoidance of drugs that release histamine or activate the sympathetic nervous system may also prevent intraoperative crises.

The head and neck cancer patient should be in the best possible medical condition before facing surgery, bearing in mind the status of the tumor and the urgency of the procedure. Careful assessment of the patient's upper airway will enable the anesthesiologist to select an appropriate course of action to secure the airway before the operation begins. In many cases, the patient can be safely intubated after the induction of general anesthesia. In other situations, the patient may require an examination of the airway while awake with the aid of sedation and topical analgesia to determine the safest intubation technique. If the patient has evidence of a difficult airway, a flexible fiberoptic-guided intubation may be indicated to secure the airway in the awake patient patient before general anesthesia is induced. Some patients with severe airway obstruction or large, bulky supraglottic tumors usually undergo an initial tracheostomy with local anesthesia to secure the airway. Following surgery, extubation of the patient's trachea requires careful attention and may have to be performed over a jet-ventilating stylet.

The efficacy of epidural hydromorphone alone or in combination with epinephrine for postoperative analgesia was evaluated in 30 healthy women who underwent cesarean delivery with epidural anesthesia. They were assigned randomly to receive either 1.5 mg hydromorphone alone (N = 15) or 1.5 mg hydromorphone with 1/200,000 epinephrine (N = 15). Duration of analgesia (mean +/- SD) was 24.3 +/- 9.4 hours after the epidural injection of hydromorphone plus epinephrine. This was significantly greater (p less than 0.01) than the duration of 18.2 +/- 5.9 hours after the same dose of plain hydromorphone. Analgesia was more rapid in onset and significantly better at the 0.5, 1, 3, and 12 hours postoperatively in the hydromorphone-epinephrine group. Side effects including pruritus (73%), nausea (20%), and vomiting (15%) were of similar frequency with and without epinephrine. Although mean venous PCO2 (PvCO2) levels three and six hours after the hydromorphone-epinephrine dose were elevated significantly over the pre-drug PvCO2 levels, no respiratory depression was detected by an apnea monitor to which all patients were connected. The addition of epinephrine to epidural hydromorphone hastened onset and prolonged the duration of analgesia after cesarean section.