Nitrogen metabolism and lipid peroxidation during hyperthermic perfusion of human livers with cancer.

Isolation-perfusion was used as a means of heating human livers with cancer. Perfusion was at 42-42.5 degrees C for 4 h. Perfusate constituents were analyzed in an attempt to identify factors contributing to the hepatotoxic effects of hyperthermia. During perfusion the perfusate constituents analyzed were: urea; total amino acids; uric acid; malonaldehyde; and lysosomal enzymes. Hepatic ammonia for urea synthesis is derived from degradation of amino acids, amines, and nucleic acids. An increase in proteolysis was reflected in the increase in urea from 0.6 +/- 0.2 mM to 1.9 +/- 8 mM and total amino acids from 1.0 +/- 0.6 mM to 4.4 +/- 1.7 mM during the 4 h of perfusion at 42-42.5 degrees C. An increase in purine catabolism occurred as evidenced by an increase in perfusate uric acid from 1.7 +/- 1.0 mg/100 ml to 6.1 +/- 2.7 mg/100 ml. Free oxygen radicals, which can lead to lipid peroxidation, are generated by the action of xanthine oxidase on xanthine. Lipid peroxidation occurring during perfusion was assessed by an increase in malonaldehyde from 2.3 +/- 1.3 microM to 10.4 +/- 10.0 microM. An increase in acid phosphatase in the perfusate from 38 +/- 15 units/liter to 78 +/- 45 units/liter occurred, suggesting labilization of lysosomes, perhaps through lipid peroxidation. Proteolysis and lipid peroxidation are suggested to be two interrelated factors contributing to heat toxicity in the perfused human liver with cancer.

Influence of inflation and atelectasis on the hypoxic pressor response in isolated dog lung lobes.

Apnoeic left lower lobes of dog lungs were inflated by increasing alveolar pressure or decreasing pleural pressure, or the lobes were collapsed and exposed to decreasing pleural pressure with the bronchus occluded. Under each of these conditions the lobe could be made 'hypoxic' by perfusion with mixed venous blood or 'normoxic' by perfusion with systemic arterial blood. Inflation of the lobes diminished the hypoxic presor response. The relative influence of decreasing pleural pressure on inflated and collapsed lobes was such that at low pleural pressures resistance to flow through the hypoxic atelectatic lobe was no greater than that through the inflated normoxic lobe. The results indicated that the level of lung inflation can alter the effectiveness of the hypoxic pressor response in reducing perfusion to underventilated regions.

Treatment of Hickman catheter sepsis using antibiotic lock technique.

Antibiotic lock therapy, an alternative treatment for Hickman catheter sepsis, was evaluated in six recipients of prolonged outpatient intravenous therapy. Twenty-two episodes of catheter sepsis were identified, involving coagulase-negative staphylococci (11), gram-negative bacilli (3), gram-positive bacilli (1), yeast (4), and mixed bacteria or fungi (3). In a select group of patients, treatment was successful 92% of the time.

Assessing the risk of blood exposure in the operating room.

During the past 3 years, a great deal of new information has been published on the risk of blood exposure and injury in the operating room. In addition, detailed information about the effectiveness of barrier materials, operating room garments, and gloves has also become available. On the basis of this information, it has become possible to recommend strategies, barrier materials, and garments that should reduce the risk of contracting a blood-borne infection in the operating room. Further attempts to decrease the risk of blood exposure and injury require thorough evaluation of all risk-reduction strategies and careful selection of protective apparel and barriers on the basis of well-designed studies performed in the operating room environment.

Cryotherapy extends the indications for treatment of colorectal liver metastases.

BACKGROUND: Hepatic resection for colorectal metastases has been established as the best option for patients with 4 or less lesions meeting specified criteria. Recently, the use of intraoperative ultrasound has increased the detection of previously occult liver lesions, and cryotherapy has allowed the treatment of liver lesions in inaccessible areas with less destruction of normal liver in the case of multiple lesions. 14e prospectively performed hepatic resection or cryotherapy to test the hypothesis that more than 4 liver metastases could be safely and successfully treated with improved long-term survival. METHODS: From August 1993 to January 1999, 137 patients with liver metastases from colorectal cancer were treated with hepatic resection or cryotherapy at the Medical College of Wisconsin. Preoperative and postoperative computed tomography scans, intraoperative assessments of lesion number and curability, number of blood transfusions administered, length of stay, complications experienced, and overall survival rates were reviewed. RESULTS: One hundred thirty-seven patients were explored. Treatment consisted of resection alone in 34, cryotherapy alone in 20, both treatments in 52, and no treatment was possible in 31 patients. "Curability" was defined as complete resection or cryotherapy of all identifiable tumor at the conclusion of the operation. A Cox proportional hazards model demonstrated that survival was determined by the destruction of all identifiable metastases (P < . 001) and was not statistically influenced by age, gender type of therapy, or the number of metastases treated. CONCLUSIONS: Surgical treatment of colorectal liver metastases remains the best option for patients with this disease. A key factor in overall survival is the destruction or resection of all identifiable disease and not the number of tumors per se. Using cryotherapy as an addition to the surgical arsenal, patients previously deemed unresectable because of the number of lesions have a chance for long-term survival. This study demonstrates improved long-term survival for "cured" patients with more than 4 metastatic lesions, thereby extending the indications for resection/ablation.

Hepatocellular carcinoma: multimodality management.

BACKGROUND: Hepatocellular carcinoma is one of the most common tumors worldwide. Surgical resection has been the standard treatment but can only be applied to a small percentage of patients. In recent years, several other treatment options, including ablative procedures and transplantation, have been used in patients with hepatocellular carcinoma. METHODS: For 6 years, 110 patients with hepatocellular carcinoma were managed at the Medical College of Wisconsin. Fifty-five patients received only chemotherapy (n = 5) or palliative treatment (n = 50) because of advanced cirrhosis (P <.03) or tumor. Thirty-one patients had tumor ablation with percutaneous ethanol injection, cryoablation, radiofrequency ablation, or arterial chemoembolization. Twenty-eight patients underwent surgical resection (n = 18) or hepatic transplantation (n = 10). Relatively more patients (38%; P <.001) were treated with ablation in the second period of the study (1998-2000). RESULTS: Thirty-day mortality was 3% with ablation and 0% with resection. Median survival was 6 months with no treatment, 27 months with ablation (P <.001), and 35 months with resection (P <.001). Patients who underwent liver transplantation had the longest median survival (53 months). A multivariate analysis suggested that treatment modality (ablation or resection; P <.001) and Child-Pugh classification (P <.01) were the most important factors predicting outcome. CONCLUSIONS: This study suggests that treatment of hepatocellular carcinoma requires multidisciplinary expertise and that ablation and operation can be performed safely. Outcome is influenced most by treatment modality and Child-Pugh classification. Patients in Child-Pugh classes A and B should be treated with ablation, surgical resection, or liver transplantation.

Pulmonary artery pressure monitoring in the surgical intensive care unit. Benefits vs difficulties.

The process of pulmonary artery pressure monitoring in 50 consecutive patients in the surgical intensive care unit was analyzed to determine the number and types of problems that occurred in relation to the benefit obtained. Twenty-six percent of the patients had a change in their cardiorespiratory therapy and their conditions were improved after the pressure data were obtained. Many technical and interpretative problems that tended to decrease the desirability of using pulmonary artery pressure monitoring were identified. Most problems could be avoided by carefully calibrating the monitor system, clearing the catheter system of air bubbles and blood clots, learning to property interpret pulmonary artery pressure tracings despite large respiratory variations, and obtaining a hard-copy printout of the pressure tracing with the simultaneous ECG signal. A protocol for avoiding many difficulties was developed.

Tumoricidal effects and patient survival after hyperthermic liver perfusion.

Hyperthermic liver perfusion for four hours at 42.0 degrees C to 42.5 degrees C was used as the sole modality of therapy for cancer confined to the liver in eight patients. Two patients had melanoma, one had cholangiolar carcinoma of the liver, and five had liver metastases from colorectal carcinoma. Two postoperative deaths occurred, both in patients with colorectal carcinoma metastases. Response was indicated by computed tomographic and/or liver biopsy or autopsy findings of tumor necrosis. There were five responders to hyperthermic liver perfusion among the six survivors. Hyperthermic liver perfusion was an effective tumoricidal agent for hepatic metastases from colorectal cancer; ie, tumor necrosis occurred in all five patients, as well as in the two who died, as shown by autopsy findings. Conversion to a disease-free state with hyperthermic perfusion may be possible with other treatment modalities used in combination or sequence.

Estimating energy requirements in patients receiving parenteral nutrition.

Adequate nutritional support should use a patient's energy expenditure as a guide for administering sufficient but not excessive caloric intake. Sixty-seven patients were evaluated using indirect calorimetry, to determine the applicability of commonly used predictive equations for energy expenditure in patients requiring parenteral nutrition. The frequently used calculation that involves multiplying a constant value of kilocalories per kilogram by the patients weight consistently underestimated the energy requirements of patients of low body weight and overestimated the requirements for heavy body weight. The Harris-Benedict equation was found to be highly dependent on body weight and was not any more accurate than estimations of individual requirements using a simpler weight or surface area regression equation. We recommend that an actual regression equation incorporating body weight or body surface area be used to predict energy requirements and that the oversimplified but common use of the constant value of kilocalories per kilogram be abandoned.

Double gloving. Protecting surgeons from blood contamination in the operating room.

Health care workers, particularly surgeons, understand the importance of preventing contamination from blood of patients infected with deadly viruses. One of the most common areas of contamination is the hands and fingers due to the failure of glove protection. There are varying opinions regarding the frequency of glove failure, the necessity of wearing two gloves for added protection, and the ability to operate when wearing two gloves. We performed a prospective, randomized, trial of 143 procedures involving 284 persons to answer these questions for surgeons and first assistants. Overall, the glove failure rate (blood contamination of the fingers) was 51% when one glove was worn and 7% when two gloves were worn. Acceptability was 88% in the group who agreed to wear two gloves, and 88% of these did not perceive that tactile sense was significantly impaired. We believe that double gloving should be, and can be, used routinely during major surgical procedures to protect surgeons from blood contamination.

A quality control analysis of aminoglycoside management.

Aminoglycoside administration practices were evaluated in a teaching hospital using three study methods: a chart review of 40 randomly selected patients receiving aminoglycosides was conducted retrospectively; 93 health care personnel involved in ordering and administering aminoglycosides to patients were interviewed regarding their understanding of aminoglycoside utilization practices; and ten patients having serum peak and trough aminoglycoside determinations were closely monitored for accuracy of dose administration and obtaining blood specimens at appropriate times. The chart review showed that during 15 of 32 evaluable therapy courses no determinations of serum aminoglycoside concentration were obtained. The survey demonstrated that only 24% of the residents actually used the results of peak and trough determinations to adjust dosage regimens. Direct observation of health care personnel disclosed only two of ten instances in which doses were administered and serum concentration specimens obtained with no apparent problems. Most personnel in our hospital were unaware of these pervasive suboptimal or inconsistent practices associated with aminoglycoside administration and interpretation of laboratory results.

Ablation of liver metastasis: is preoperative imaging sufficiently accurate?

The recent introduction of cryotherapy and radiofrequency ablation of liver metastasis has expanded the indications for treatment. As technology has advanced, a percutaneous approach has been developed. Percutaneous treatment, however, requires accurate preoperative imaging. From 1993 to 1999, 179 patients underwent operative exploration for treatment of suspected hepatic metastases from colorectal carcinoma. One hundred seventy-seven patients were staged by preoperative CT, two patients were staged by MRI, and complete data were available in 176. Hepatic tumor count by preoperative imaging was compared to intraoperative tumor count obtained by inspection, palpation, ultrasonographic examination using a 3.5/7.5 MHz T probe, and careful gross sectioning of the resected specimen. Post hoc analysis was performed on 35 CT scans by two radiologists who specialize in abdominal CT. These radiologists were blinded to the intraoperative findings. Their interpretations were compared to the intraoperative counts and to each other. Thirty-four (19%) of 179 patients were deemed untreatable at operation because of unsuspected overwhelming liver involvement in 11 (6%) or extrahepatic metastases in 23 (13%). For the group, CT was accurate in 80 patients (45%), showed more lesions than were found in 16 (9%), and showed fewer metastases than were found in 80 (45%). When the preoperative scan predicted a solitary metastasis, it was correct in 45 (65%) of 69 patients and underestimated disease in 24 (35%). In the post hoc analysis, the mean numbers of lesions reported by the two radiologists did not differ from the mean number of tumors found; however, the radiologists' counts agreed on 16 (59%) and disagreed on 11 (41%) of the scans. The accuracy of CT decreased with increasing numbers of lesions. Regardless of the type of preoperative imaging, intraoperative findings altered the course of the operation in 96 (55%) of 176 patients. Preoperative imaging is not sufficiently accurate to permit adequate percutaneous treatment of hepatic metastases from colorectal carcinoma.

Analysis of pain management in critically ill patients.

We analyzed the adequacy of pain control for 17 trauma patients during the initial part of their stay in the intensive care unit, and assessed reasons for inadequate analgesia, if it occurred. Patients, and physicians, and nurses were interviewed. A verbal pain intensity scale was used to determine whether patients received adequate analgesia. Patients were asked if the pain hindered their activities, and whether they requested pain medication from their caregivers. Caregivers were questioned whether patients received adequate analgesia. Prescribed morphine regimens and the amount of narcotic administered were analyzed. Twenty-seven percent of patients rated pain intensity as moderate and 47% as severe. Ninety-five percent of housestaff and 81% of nurses reported the patients received adequate pain control. Forty-seven percent of the patients who had moderate or severe pain asked their physician for more pain medication, and 65% asked the nurse. Thirteen residents did not order a larger dose of morphine due to concern about respiratory depression or hypotension. Morphine dosages ranged from 1-8 mg intravenously every 1-2 hours as necessary. Nurses administered less than the maximum amount ordered 58% of the time. The mean dosing interval was 2.3 hours. Barriers to adequate pain management were disparity in the perception of pain between patients and caregivers; patients not requesting more analgesia despite despite the presence of moderate to severe pain; and physician and nurse concerns about patients' adverse physiologic response to increased dosages.

Pharmacokinetic evaluation of a new oral cyclosporine formulation.

STUDY OBJECTIVE: To compare the pharmacokinetics of a new oral cyclosporine preparation with those of cyclosporine solution diluted in Isocal and the intravenous formulation. DESIGN: Randomized, crossover trial. SETTING: Tertiary care referral center. PATIENTS: Seven pediatric liver transplant recipients who were receiving oral cyclosporine as part of their immunosuppressive regimen. All patients completed the study. INTERVENTIONS: Pharmacokinetic studies were performed with the intravenous and oral dosage forms. Patients received one dose of intravenous cyclosporine, and then were randomized to receive their usual oral cyclosporine dose incorporated into a chocolate wafer or mixed with Isocal. After a minimum of 3 days, the alternative preparation was administered. Serial cyclosporine blood samples were collected at predetermined intervals for 12 hours after the third dose for each regimen. Concentrations were determined by high-performance liquid chromatography. The data for the three dosage forms were fit simultaneously with a two-compartment model. MEASUREMENTS AND MAIN RESULTS: No difference was seen in F, ka, Cmax, and tmax between the two oral cyclosporine preparations (p > 0.05). No new rejection episodes occurred during the study period. CONCLUSIONS: We conclude there is no difference in the bioavailability of the oral solution and the chocolate formulation. We believe the new preparation may increase patient compliance and ensure administration of a complete dose compared with the currently marketed solution.

Current patterns of prescribing and administering morphine in trauma patients.

We attempted to characterize the current prescribing practices and administration patterns for intravenous intermittent morphine in trauma patients in a multicenter, open prospective, observational study. The subjects were 141 patients admitted to the surgical intensive care units (ICU) of five United States trauma centers within 12 hours of injury who received intermittent intravenous morphine for pain relief. The study was conducted from April 15, 1992, to February 15, 1993. Data obtained during the first 32 hours of the ICU stay included morphine regimen, doses administered, and time between doses. One hundred sixty-one orders were prescribed by surgeons. The most frequently ordered dose was 2-4 mg and the most frequently ordered interval was every hour as necessary. There was no relationship between the severity of injury and the minimum dose ordered. During the 492 nursing shifts studied, 1257 doses were administered. Of these, 44% were at or below the minimum amount prescribed by the surgeons. Thirty-three percent of the patients received a dose at an interval of more than 3 hours. We concluded that small amounts of narcotic analgesics are given to severely injured patients, and amount ordered is not affected by the severity of injury.

Postoperative atrial fibrillation in noncardiothoracic surgical patients.

BACKGROUND: Atrial fibrillation is a common arrhythmia whose prevalence increases with age. It is a well-known complication of cardiothoracic surgery, but the incidence and contributing factors to the development of atrial fibrillation in noncardiothoracic surgical patients are less well known. This study was undertaken to investigate the incidence, association with known risk factors, treatment, and outcome of atrial fibrillation in postoperative noncardiac, nonthoracic surgical patients. METHODS: A 2-year retrospective review was performed of all noncardiac, nonthoracic surgical patients that developed atrial fibrillation within 30 days of operation. Incidence, risk factors, treatment and outcome related to the development of this arrhythmia were analyzed. RESULTS: Fifty-one patients developed atrial fibrillation during this study period for an incidence of 0.37%. Most had preexisting cardiac risk factors, a positive fluid balance, or had electrolyte or arterial oxygen saturation abnormalities. Two thirds were discharged home on new cardiac medications, 16% remained in atrial fibrillation, and 12% died. CONCLUSIONS: New onset atrial fibrillation in this group of noncardiothoracic surgical patients is an uncommon problem that is a morbid event associated with significant mortality.

Care of the trauma patient in the age of the human immunodeficiency virus.

HIV-infected patients will be seen in emergency rooms and trauma centers because the number of infected patients is large and growing. Proper precautions by health care workers are effective in decreasing risk of transmission to a very low level, and, therefore, the fear of HIV should not dissuade the medical profession from giving these individuals proper care. Operative treatments should not be arbitrarily rejected simply because an HIV infection is detected because poor wound healing and infection appear to be much less of a risk than predicted. Unusual infections and intercurrent medical problems may require additional attentiveness to detect their existence and may require more complex treatment regimens to control.

How to select and evaluate new products on the market.

New devices and products often promise to protect health-care workers and patients from transmission of viral infections. These need to be evaluated carefully for efficacy, applicability, and cost in an objective, structured manner.

Hand protection.

The traditional purpose of surgical gloves is to prevent transmission of pathogens (usually bacterial) from surgeon to patient. Yet the hand is also the most common site of injury and blood contamination among operating room personnel. Thus, gloves also can protect against transmission of pathogens from patient to surgeon. This article focuses on the value of gloves for hand protection. The current data on such protection derive exclusively from studies that use glove leak and contamination as outcome measures. There are no data that measure protection in terms of actual disease transmission.

Aminoglycoside serum concentration sampling via central venous catheters: a potential source of clinical error.

Two patients receiving aminoglycosides via central venous Silastic catheters were noted to have serum drug concentrations markedly divergent from expected results. Study of these patients, and of four additional patients prospectively selected for study, demonstrated that three of five patients had higher peak and/or trough aminoglycoside serum concentrations--when blood was obtained from the central venous catheter--than were contained in simultaneous samples from peripheral blood; these divergent results were noted after the catheter had been in use for more than 1 week; divergent results were not improved by additional catheter flushing prior to central venous blood sampling. These observations suggest that spurious aminoglycoside serum concentration results may sometimes be obtained when blood sampling is performed from central venous Silastic catheters, and can result in improper drug dosage alterations. It is necessary to access the timing, processing, and reliability of serum drug-monitoring practices on a routine basis to preclude such problems, and to reassess individual patient-monitoring studies which are inconsistent with anticipated results.