Association between neuraxial analgesia, cancer progression, and mortality after radical prostatectomy: a large, retrospective matched cohort study.

BACKGROUND: Systemic opioids are immunosuppressive, which could promote tumour recurrence. We, therefore, test the hypothesis that supplementing general anaesthesia with neuraxial analgesia improves long-term oncological outcomes in patients having radical prostatectomy for adenocarcinoma. METHODS: Patients who had general anaesthesia with neuraxial analgesia (n=1642) were matched 1:1 based on age, surgical year, pathological stage, Gleason scores, and presence of lymph node disease with those who had general anaesthesia only. Medical records were reviewed. Outcomes of interest were systemic cancer progression, recurrence, prostate cancer mortality, and all-cause mortality. Data were analysed using stratified proportional hazards regression, the Kaplan-Meier method, and log-rank tests. The median follow-up was 9 yr. RESULTS: After adjusting for comorbidities, positive surgical margins, and adjuvant hormonal and radiation therapies within 90 postoperative days, general anaesthesia only was associated with increased risk for systemic progression [hazard ratio (HR)=2.81, 95% confidence interval (CI) 1.31-6.05; P=0.008] and higher overall mortality (HR=1.32, 95% CI 1.00-1.74; P=0.047). Although not statistically significant, similar findings were observed for the outcome of prostate cancer deaths (adjusted HR=2.2, 95% CI 0.88-5.60; P=0.091). CONCLUSIONS: This large retrospective analysis suggests a possible beneficial effect of regional anaesthetic techniques on oncological outcomes after prostate surgery for cancer; however, these findings need to be confirmed (or refuted) in randomized trials.

Obesity trends in the surgical population at a large academic center : a comparison between 1989-1991 to 2006-2008 epochs.

BACKGROUND: Changes in the prevalence of obesity of surgical patients overtime and in relation to the general population have not been well characterized. METHODS: Height, weight, age and gender data of adult patients who underwent general anesthesia at our institution were abstracted. Reliable data was available for the years 1989-1991 and 2006-2008, and comparisons were made between these epochs. Additional comparisons were made between our Minnesota surgical patients and the general Minnesota population. RESULTS: Substantial changes in patient weight occurred with a decline in normal weight patients (body mass index [BMI] < or =25.0) from 41.6% to 30.9% (P <0.001), while the prevalence of obesity (BMI 30-34.9) increased from 14.9% to 20.6% (P <0.001) and morbidly obesity (BMI > 35) from 7.1% to 14.8% (P <0.001). Minnesota surgical patients had a higher prevalence of obesity in every demographic category (P <0.001) compared to the general population. CONCLUSION: A substantial increase in the prevalence of obesity and morbid obesity among surgical patients at our institution occurred and the prevalence of obesity in our contemporary practice is higher than the general population. These observations most likely have profound implications on healthcare delivery resources, though its impact has yet to be determined.

The effects of continuous glucose infusion on blood, plasma, and brain glucose in anesthetized rats.

In models of cerebral ischemia, it is important to rigidly control brain glucose in the peri-ischemic period because alterations in brain glucose can affect the severity of the postischemic injury. The following study evaluated the effect of a continuous glucose infusion as a means of producing stable increases in brain glucose that could be monitored by measuring either blood or plasma glucose. Fifty-four halothane-anesthetized rats were studied. Rats received either no treatment (control group; N = 6), saline 2 ml/h (N = 24), or glucose 1 g/kg per h in saline 2 ml/h (N = 24). In the latter two groups, samples of blood, plasma, and brain glucose were obtained at either 30, 60, 120, or 180 min of the infusion (N = 6 per group per sample period). Saline infusion had no effect on either blood, plasma, or brain glucose. In contrast, glucose infusion produced a significant increase in all three variables, achieving plateau increases during the 60-180 min measurement periods [blood glucose = 197 +/- 20 mg/dl (mean +/- S.D.) at 60 min, 220 +/- 34 mg/dl at 120 min, and 217 +/- 22 mg/dl at 180 min versus control blood glucose = 89 +/- 10 mg/dl]. Regardless of the treatment group, there was excellent correlation between blood and plasma glucose (r = 0.99; P much less than 0.001), blood and brain glucose (r = 0.96; P much less than 0.001), and plasma and brain glucose (r = 0.97; P much less than 0.001). The authors conclude that continuous glucose infusions are an effective method to produce stable increases in brain glucose in experimental models; and, in contrast to other methods for achieving brain glucose increases, the brain glucose increases can be accurately assessed by measuring blood or plasma glucose.

Study of direct variable anesthesia costs in the dilatation and curettage patient.

This retrospective study was designed to compare the cost of anesthesia in three different groups of patients who received general anesthesia for a diagnostic dilatation and curettage procedure. The analysis included 194 patients, ASA physical status I, II, or III. All patients were outpatients with similar body mass index and age. The three groups were thiopental/isoflurane (n = 13), propofol/isoflurane (n = 126), and propofol/desflurane (n = 55). Anesthesia drugs, volatile agents, personnel costs, and type of providers were included in the cost comparison. The cost of supplies, inhalation agents, and drugs for the thiopental/isoflurane group were significantly different (P < .001) than the other two groups. The mean +/- SD thiopental/isoflurane combination was $7.00 +/- $2.74, whereas, the mean +/- SD cost of the propofol/isoflurane and propofol/desflurane groups was $12.73 +/- $3.57 and $14.40 +/- $5.05, respectively. The mean +/- SD cost of all three anesthetic drugs/volatile agents/endotracheal tube groups was $12.85 +/- $4.35. No statistically significant differences between the three groups were found in postanesthesia care unit (PACU) drug costs, anesthesia personnel cost, total direct anesthesia costs, or length of stay. The incidence of antiemetic administration intraoperatively and in PACU was significantly different (P < .001) between the thiopental/isoflurane group and the other groups. The thiopental/isoflurane group did not receive any antiemetics in either area, whereas the propofol groups received antiemetics 12.7% of the time. The three anesthesia providers, Certified Registered Nurse Anesthetists, student registered nurse anesthetists (SRNA), and anesthesia residents were reviewed looking at anesthesia supply cost, personnel cost, and total direct anesthesia costs. No statistically significant differences were found between the groups. We conclude that an anesthetic using thiopental/isoflurane is more cost-effective than propofol/desflurane or propofol/isoflurane anesthetics and the postoperative length of stay is no different for the three anesthetic approaches.

The effects of insulin infusion on plasma and brain glucose in hyperglycemic diabetic rats. A comparison with placebo-treated diabetic and nondiabetic rats.

Experimental and clinical studies have revealed a worsened neurologic outcome after cerebral ischemia in hyperglycemic subjects, including hyperglycemic diabetic subjects. A possible therapy to reduce the magnitude of ischemic brain injury in diabetic subjects would be to use an insulin infusion to reduce brain glucose concentrations to values found in those who are normoglycemic and non-diabetic. The present study, using hyperglycemic diabetic rats, examined the effect of an insulin infusion on plasma and brain glucose concentrations to determine their relationship while plasma glucose concentrations decreased. In addition, plasma and brain glucose concentrations were compared to those in diabetic and nondiabetic rats treated with saline. Saline had no effect on the plasma or brain glucose concentrations in the diabetic rats or nondiabetic rats. The saline-treated diabetic rats had increased plasma and brain glucose concentrations as well as an increased brain-to-plasma glucose ratio when compared to the saline-treated nondiabetic rats. When an insulin infusion was used in diabetic rats to decrease plasma glucose to nondiabetic levels over approximately 2 h, the brain glucose concentration decreased. However, the brain-to-plasma glucose ratio remained at the "diabetic" value, so that the brain glucose concentration tended to remain increased when compared to normoglycemic, nondiabetic rats. We conclude that if these results are applicable to humans, measurement of plasma glucose in diabetic patients will underestimate the amount of glucose in the brain and this relationship will not be influenced by acute insulin therapy.

Effects of insulin on blood, plasma, and brain glucose in hyperglycemic diabetic rats.

This study, in biologically bred hyperglycemic diabetic rats, examined the effect of a intravenous insulin infusion (1.5 units.hr-1) on blood, plasma, and brain glucose concentrations to determine their relationship during decreasing blood and plasma glucose levels. The data were compared to saline-treated diabetic rats and saline-treated nondiabetic littermates. The volume and duration of the treatment infusion were similar in all groups. Insulin infusion in diabetic rats produced the expected reduction in blood and plasma glucose, and normoglycemia was produced within 78 +/- 37 minutes (mean +/- SD). However, once normoglycemia was achieved, brain glucose was still significantly greater by 44% than in nondiabetic rats (p = 0.015). Moreover, the ratio of brain to plasma glucose was more than 50% greater in diabetic than nondiabetic rats, irrespective of whether or not they received insulin (p less than 0.01). We conclude that measurement of blood or plasma glucose in diabetic subjects will tend to underestimate the amount of glucose in the brain and that this relationship is not influenced by acute insulin therapy.

Effect of hydroxyethyl starch solutions on blood glucose concentrations in diabetic and nondiabetic rats.

BACKGROUND AND METHODS: The effects of iv infusions of 6% hetastarch or 10% pentastarch on blood glucose concentrations were tested in 12 nondiabetic and 12 streptozotocin-induced diabetic pentobarbital-anesthetized Sprague-Dawley rats weighing 313 to 473 g. All rats were paralyzed and mechanically ventilated. After control measurements of blood glucose concentrations were taken, rats were divided into four groups. Groups 1 (n = 6) and 2 (n = 6) comprised nondiabetic rats that received iv infusions of hetastarch or pentastarch, respectively, at a rate of 2.0 mL over 30 mins. Groups 3 (n = 6) and 4 (n = 6) comprised diabetic rats that also received iv hetastarch or pentastarch, respectively, at the same rate and duration of infusion. RESULTS: Neither hetastarch nor pentastarch infusions significantly altered blood glucose values over the 3-hr study period, regardless of whether the rats were diabetic or nondiabetic. CONCLUSIONS: Assuming these data are transferable to humans, the authors conclude that hydroxyethyl starch solutions do not produce or exacerbate hyperglycemia, and furthermore, that their use is not contraindicated in subjects having hyperglycemia from diabetes mellitus or iatrogenic causes.

Norepinephrine does not potentiate porcine malignant hyperthermia.

Malignant hyperthermia (MH) is a rare genetic trait characterized by potential life-threatening episodes of hypermetabolism, hyperthermia, and muscle rigidity when susceptible humans or animals are exposed to triggering drugs. The role of norepinephrine (NE) in triggering MH is controversial. The purpose of this study was to show that NE does not initiate nor speed the onset of MH in susceptible swine exposed to known triggering drugs. Three groups of MH susceptible (MHS) pigs were exposed to two times the minimum alveolar anesthetic concentrations (MAC) halothane (2%) for 60 min and monitored continuously until a PaCO2 of 70 mm Hg was obtained as an end point for fulminant MH. This dose of halothane is associated with significant hypotension which was addressed by three modalities: no treatment; NE infusion at 8 micrograms.kg-1.min-1; and intraaortic balloon pump (IABP) with 1:1 augmentation (7.0-mL balloon catheter). NE and epinephrine (Epi) plasma levels were determined at 15-min intervals and at trigger time. All animals developed signs of MH during the study. There was no difference in pHa, lactate, PaCO2, or temperature at control or trigger times between groups. Time to trigger was longer in the untreated group compared to both the NE and the IABP groups which were equal. The NE group had greater NE and Epi plasma levels at all times than either the untreated or IABP group and the levels increased at each sample time. The IABP group had increased NE levels at time of trigger compared to control time period, however, Epi levels did not increase. In the untreated group, individual animals had marked increases in NE levels, but extreme variability in response prevented achievement of a single mean change. This group showed no increase in plasma Epi levels throughout the study. There was no difference in NE levels between the untreated and IABP groups. Three animals in the untreated group died prior to trigger due to complications of hypotension. In conclusion, addition of exogenous NE in high doses did not enhance triggering of MH. The large dose NE infusion resulted in increased total catecholamines throughout the study in the NE group with no effect on time to MH trigger compared to animals where mean arterial pressure (MAP) was maintained by IABP. Animals in all three groups with times to trigger of less than 30 min had significantly higher MAPs at control, 15 min, and trigger time than those with times to trigger of greater than 30 min. We conclude that NE does not trigger MH and that severe reduction of MAP delays the the onset of MH in susceptible swine.

Metabolism of glucose, glycogen, and high-energy phosphates during transient forebrain ischemia in diabetic rats: effect of insulin treatment.

BACKGROUND: Hyperglycemia associated with diabetes mellitus will exacerbate neurologic injury after global brain ischemia. Studies in a rat model of forebrain ischemia (bilateral carotid occlusion plus hypotension for 10 min) discovered that acute restoration of normoglycemia in diabetics, using an insulin infusion, resulted in a neurologic outcome that was similar to normoglycemic rats without diabetes. The current study evaluated cerebral glucose, glycogen, lactate, and high-energy phosphate concentrations to identify metabolic correlates that might account for an alteration in postischemic outcome. METHODS: Fifty-four pentobarbital-anesthetized Sprague-Dawley rats were assigned to three groups: chronically hyperglycemic diabetic rats (D; N = 18); insulin-treated, acutely normoglycemic diabetic rats (ID; N = 18); and nondiabetic rats (ND; N = 18). These groups were further divided into groups of six rats each that received either no ischemia, forebrain ischemia of 10 min duration without reperfusion, or ischemia plus 15 min of reperfusion. Brains were excised after in situ freezing, and metabolites were measured using enzymatic fluorometric techniques. RESULTS: Before ischemia, D rats had greater concentrations of brain glucose (12.18 +/- 2.67 micromol/g) than did either ID (5.10 +/- 1.33) or ND (3.20 +/- 0.27) rats (P < 0.05). Preischemic brain glycogen was similar in all groups. At the completion of ischemia, brain lactate concentrations in D were 86% greater than in ID and 61% greater than in ND (P < 0.05), reflecting a higher intraischemic consumption of glucose plus glycogen in D (P < 0.05). High-energy phosphate concentrations, as assessed by the energy charge of the adenylate pool, were better preserved in D (energy charge = 0.60 +/- 0.28) than in either ID (0.29 +/- 0.09) or ND (0.36 +/- 0.07; P < 0.05) rats. After 15 min of reperfusion, the energy charge returned to preischemic values (i.e., 0.91-0.92) in all groups. CONCLUSIONS: These studies demonstrated greater intraischemic carbohydrate consumption and lactate production in D than in ID or ND rats. Under these conditions, intraischemic-but not postischemic-energy status was better in D rats. Acute insulin therapy in ID rats resulted in a metabolic profile that was similar to that of ND rats. These results suggest that, in this model, primary energy failure during ischemia is not the origin of greater injury in hyperglycemic diabetics, nor is energy enhancement the origin of improved outcome after acute insulin treatment.

The temporal relationship between intraocular pressure and extraocular muscle activation in cats.

The temporal relationship between intraocular pressure and extraocular muscle activation was studied in cats in response to the administration of the depolarizing muscle relaxant, succinylcholine (i.e. bolus doses of 0.1 and 1.0 mg/kg). Simultaneous changes in intraocular pressure, extraocular muscle force, extraocular electromyograms (EMGs), limb muscle EMGs and hindlimb muscle afferent activity were recorded. Increases in intraocular pressure were associated with extraocular muscle activation and had two components: (1) an initial abrupt increase (lasting seconds) which correlated with fasciculations within the extraocular and hindlimb muscles; and (2) a latter more sustained component (minutes) presumably due to tonic muscle activation which correlated with increases in hindlimb muscle afferent activity (e.g. due to sustained activation of bag 1 intrafusal fibers by succinylcholine). In a separate group of animals, in which the extraocular muscles were detached from the right eye bilateral intraocular pressures were measured: depolarization by succinylcholine caused a significant increase in intraocular pressure only for the eye with intact muscles. Thus, increases in intraocular pressure following the administration of succinylcholine are directly related to the changes in extraocular muscle tension which is dependent on both tonic and phasic muscle fiber responses.

The effect of a platelet activating factor antagonist (BN 52021) on neurologic outcome and histopathology in a canine model of complete cerebral ischemia.

BACKGROUND: Research has demonstrated that platelet activating factor may modulate, in part, the severity of postischemic neurologic injury. The proposed mechanism involves a platelet activating factor-mediated release of cerebral cellular lipids and free fatty acids, resulting in increased cerebral edema and cell injury. The present study tested the hypothesis that a specific platelet activating factor antagonist, BN 52021, would improve neurologic outcome after 12 min of complete global cerebral ischemia in a canine model. METHODS: Using an established canine model of complete cerebral ischemia, dogs were assigned randomly to receive, in a blinded fashion, either 20 mg/kg BN 52021 intravenously (N = 8) or placebo (N = 7) 5 min before cerebral ischemia. After cerebral ischemia and recovery, neurologic assessment was performed by a blinded observer for 72 h. Immediately thereafter, the brains were harvested and later were evaluated histologically by a neuropathologist blinded to the treatment groups. RESULTS: Dogs were well matched for systemic physiologic variables during all portions of the study. One placebo-treated dog and one BN 52021-treated dog were not included in the statistical analysis because of failure to meet preestablished protocol criteria. BN 52021, when compared to placebo, affected neither neurologic functional recovery nor overall histopathology scores. Regional histopathology was improved in BN 52021-treated dogs in only 1 of 18 brain regions studied (i.e., the parietal cortex). When both treatment groups were combined, there was a significant correlation between neurologic function rank and histopathology rank. CONCLUSIONS: The present data demonstrate that the platelet activating factor antagonist BN 52021, at a dose of 20 mg/kg intravenously given 5 min before cerebral ischemia, did not protect the brain from injury in this canine model of complete global ischemia.

Temperature changes of > or = 1 degree C alter functional neurologic outcome and histopathology in a canine model of complete cerebral ischemia.

BACKGROUND: Changes in basal temperature of > or = 1 degree C (e.g., fever-induced hyperthermia or anesthesia-related hypothermia) are a common occurrence in neurologically impaired patients. The current study tested the hypothesis that temperature changes as small as 1 degree C or 2 degrees C would significantly alter post-ischemic functional neurologic outcome and cerebral histopathology. The hypothesis was tested in a canine model of transient, complete cerebral ischemia. METHODS: After institutional approval, 21 dogs were randomly assigned to one of three temperature-specific groups: (1) a reference group maintained at 37.0 +/- 0.3 degree C (target temperature +/- range); (2) a 38.0 +/- 0.3 degree C group; or (3) a 39.0 +/- 0.3 degree C group (n = 7 per group). Complete cerebral ischemia 12.5 min in duration was produced using an established model of arterial hypotension plus intracranial hypertension. Right atrial and cranial (beneath the temporalis muscles) temperatures were maintained at the target value, beginning 20 min before ischemia and ceasing 1 h postischemia. Thereafter, temperatures were returned to 37.0 +/- 0.3 degree C in all dogs. After discharge from the intensive care environment, all dogs were placed in a temperature-controlled recovery area. Neurologic assessment was performed by a blinded observer at 24, 48, and 72 h postischemia using a 100-point scoring scale. After the 72 h examination (with the dogs anesthetized) or at the time of ischemia-related death, the brains were excised and preserved. The brains subsequently were histologically scored by a neuropathologist who was unaware of the treatment groups. All 21 dogs were included in the analysis of neurologic function; however, only dogs that survived for > or = 24 h postischemia were included in the histopathology analysis. RESULTS: Dogs were well matched for systemic physiologic variables throughout the study, with the exception of temperature. During the 72 h postischemic examination, dogs maintained at 37 degrees C were either normal or near normal. In contrast, dogs maintained at 39 degrees C were either comatose or died from ischemia-related causes. Dogs maintained at 38 degrees C were intermediate between 37 degrees C and 39 degrees C dogs. When compared with the reference group, both 38 degrees C and 39 degrees C dogs had significantly worse neurologic function scores (P < 0.01 and < 0.001, respectively) and histopathology scores (P < 0.01 for both). There also was a significant correlation between neurologic function and histopathology rank scores (rs = 0.96; P < 0.001). CONCLUSIONS: Small, clinically relevant changes in temperature (1 degree C or 2 degrees C) resulted in significant alterations in both postischemic neurologic function and cerebral histopathology. Assuming that our results are transferable to humans, the results suggest that, in patients at imminent risk for ischemic neurologic injury, body temperature should be closely monitored. Further, the clinician should aggressively treat all episodes of hyperthermia until the patient is no longer at risk for ischemic neurologic injury.