Biomedical subjects
Publications and source records attributed to R G Hahn.
Dilutional hyponatraemia with symptoms (TUR syndrome) may occur not only in association with transurethral prostatic resection, but also in other operations in which electrolyte-free irrigating fluid is used. This case report describes a patient who developed the TUR syndrome after blood clots had been removed from the bladder with the aid of a transurethral resectoscope.
The short-term effect of epidural anaesthesia (EDA) on the serum potassium (S-K) concentration was studied in 40 elderly men scheduled for minor urological surgery. In Group I, EDA was induced with mepivacaine 2% + adrenaline 1:200,000 (n = 20) and in Group II mepivacaine 2% was used (n = 20). When EDA had been induced, the mean plasma level of adrenaline was tripled in Group I, while it had decreased in Group II. In Group I there was a decrease in the arterial S-K concentration of up to 0.75 mmol.l-1 with a mean of 0.31 mmol.l-1, s.d. 0.20 (P less than 0.001). In Group II, a small but significant decrease of the S-K level was recorded in arterial (0.14 mmol.l-1, s.d. 0.14; P less than 0.001) but not in venous serum. Two-way analysis of variance showed that the addition of adrenaline to the local anaesthetic solution, but not the choice of using arterial or venous serum for analysis, significantly correlated to the lowering of the S-K concentration (P less than 0.001).
If ethanol is added to the irrigant used during transurethral prostatic resection, the absorption of fluid can immediately be detected by measuring the ethanol concentration in the expired breath. To evaluate this method further, we studied the influence of chronic obstructive pulmonary disease (COPD) on the agreement between expired-breath and blood-ethanol concentrations. In 14 men with a mean age of 62 years (range 55-68), the concentrations of ethanol in whole blood and end-expired breath were measured at 12 exactly timed intervals before, during, and after an intravenous infusion of 0.6 g.kg-1 ethanol for 60 min. The pulmonary function was normal in seven of the subjects (control group) whereas the other seven suffered from severe COPD (study group). The results show that the accuracy and precision of breath-alcohol analysis to predict the blood-ethanol level were poorer during the infusion of ethanol than afterwards. However, at all times of sampling the estimation of blood-ethanol concentration indirectly by analysis of breath was not significantly different for COPD patients and the control group. We conclude that ethanol monitoring of irrigant absorption can be used successfully in patients with COPD.
The transurethral resection syndrome ("TUR syndrome") is caused by absorption of electrolyte-free irrigating fluid, and consists of symptoms from the circulatory and nervous systems. The clinical picture is inconsistent and the syndrome is easily confused with other acute disorders. Mild forms are common and often go undiagnosed, while severe forms of the TUR syndrome are rare and potentially life-threatening. The pathophysiology is complex but includes four mechanisms: circulatory distress from the rapid absorption of electrolyte-free irrigating fluid, adverse effects of glycine, dilution of the protein and electrolyte concentrations of the body fluids, and disturbance of renal function. The treatment of the TUR syndrome consists of general life support and in specific treatment directed towards hypotension, hyponatraemia and anuria. Methods to lower the uptake of irrigating fluid are widely used and probably reduce the incidence of the TUR syndrome. However, patient safety can be guaranteed only if the absorption is monitored. An irrigating fluid containing tracer amounts of ethanol can be used for this purpose. This permits the uptake of fluid to be indicated by measuring the concentration of ethanol in the patient's exhaled breath.
Ten male patients scheduled for transurethral prostatic resection (aged 57-79) were given irrigating fluid by intravenous infusion at 50 ml.min-1 over 20 min. Each patient was subjected to two infusions: 1.5% glycine in water on one occasion, and the same solution but with 1% ethanol added on the other. Urine and blood samples were collected at regular intervals for up to 2 h after infusion, and the changes in the distribution of water and electrolytes between fluid compartments were calculated. Transient prickling skin sensations were frequently reported effects of the infusions. Two patients experienced visual disturbances. There were no changes in the blood ammonia and plasma vasopressin levels. During the infusions, the estimated blood volume and the total plasma sodium and potassium content increased. The solutions produced osmotic diuresis with increased urinary excretion of water and electrolytes. After ending the fluid administration, blood volume was rapidly restored. Over the following 120 min the irrigant water was redistributed intracellularly or removed by urinary excretion. The addition of ethanol did not alter the overall effects of glycine solution on the fluid balance.
If ethanol is added to the irrigant used in transurethral resection of the prostate, absorption of the fluid can be immediately detected by measuring the ethanol concentration in the expired breath. During 90 resections where the irrigant contained 1.5% glycine and 1% ethanol, the breath alcohol level was compared with the amount of irrigant absorbed as determined by volumetric measurement. The results showed that the expired-breath ethanol level depended not only on the volume of irrigant absorbed but also on the rate of ethanol diffusion in the total body water, which increased with the ethanol concentration. By applying a derived mathematical model the absorption could be estimated from the breath alcohol level at any time during surgery, with a median deviation of 19% from the measured value.
In 30 patients the blood ammonia concentration was measured 30 min was after transurethral resection of the prostate during which absorption of irrigating fluid containing 1.5% of glycine and 1% of ethanol had been indicated by serial expired breath tests. The volume of irrigating fluid that had been absorbed was either measured volumetrically (n = 25) or estimated from the ethanol concentration in the expired breath (n = 5); the median volume of irrigating fluid absorbed was 1.3 litres (range 0.2-4.3). There was no consistent rise in the blood ammonia concentration, nor was there any correlation between the blood ammonia concentration and the volume of irrigating fluid absorbed. No patient developed symptoms that could be clearly related to hyperammonaemic glycine toxicity, but 18 of the 30 patients developed other signs of the "TURP syndrome". The present results suggest that irrigating fluid containing both glycine and ethanol does not significantly increase blood ammonia concentration or produce symptoms of glycine toxicity.
The plasma vasopressin and serum cortisol concentrations were recorded in 7 healthy volunteers receiving an intravenous infusion of 1 l of isosmotic (2.2%) glycine solution during 20 min. The infusion elicited a significant increase in the plasma vasopressin level by a mean of 60% (SEM 13) above baseline level. The serum cortisol level increased only in the patient who developed signs of glycine toxicity. These results suggest that a glycine solution has water-retaining properties by stimulating the vasopressin secretion but usually not by increasing cortisol secretion.
The results of a randomized, multicenter, cooperative group trial evaluating hormonal therapy with either megestrol acetate or dexamethasone in advanced, hormonally refractory prostate cancer are reported. Three of 29 patients (approximately 10%) on the megestrol acetate arm experienced an objective response lasting 41, 84, and 202 days, respectively, whereas two of 29 patients (approximately 7%) on the dexamethasone arm achieved an objective response lasting 359 and 512 days, respectively. Twenty of 29 patients (approximately 69%) on the megestrol acetate arm had stable disease lasting for a median duration of 117 days, whereas 21 of 29 patients (72%) on the dexamethasone arm had stable disease for a median duration of 86 days. Median survival of all patients was 9 months from initiation of treatment. The median survival of all patients on the megestrol acetate arm was 268 days compared to 246 days for patients on the dexamethasone arm (P = 0.2). Neither dexamethasone nor megestrol acetate would seem to be of substantive value in altering the progression of advanced, hormonally refractory prostate cancer.
Forty-eight patients with advanced gastric cancer and measurable areas of malignant disease were treated with etoposide (130 mg/m2/day X 3 days) plus cisplatin (45 mg/m2day on days 2 and 3). Both drugs were given by constant intravenous infusion and repeated every 4 weeks. Common toxic reactions included nausea, vomiting, diarrhea, alopecia, peripheral neuropathy, leukopenia, and thrombocytopenia. Most patients experienced severe but reversible toxic reactions. In 46 evaluable patients an overall objective regression rate of 28% was obtained with a median duration of regression of 4 months. Regression rates were only modestly reduced among patients with prior chemotherapy exposure (21%). Whereas this combination of etoposide and cisplatin does not appear to offer any major advantage over other single and combination regimens in the treatment of advanced gastric cancer, it shows definite activity and its lack of cross-resistance with other commonly used agents for this disease could indicate a possible role in new combination or sequential chemotherapy approaches. As an interesting sidelight, we found that 21% of our patients had elevated human chorionic gonadotropin (HCG) levels, and among this group regression rates were higher than in HCG-negative patients. It would be of interest to extend these observations in other gastric carcinoma studies involving cisplatin regimens.
Twenty-nine patients with metastatic prostate cancer progressing after hormonal therapy (orchiectomy 19, diethylstilbestrol 10) and who had never received cytotoxic therapy were treated with carboplatin. Patients had good clinical performance status (66% PS 0,1) and adequate renal (creatinine less than 2.0 mg/dL) and bone marrow function. The standard dose of carboplatin administered was 400 mg/sq m. Seventeen patients received this dose and 12 either 320 mg/sq m or 250 mg/sq m based on reduced renal function or prior radiation. Five patients had bidimensionally measurable disease: one experienced a partial regression of cervical lymph node metastases of 97 days duration. Twenty-four patients had metastatic disease evaluable by clinical status, bone scan and acid phosphatase. In one patient greater than 50% reduction in number of abnormal areas of bone scan uptake occurred; 3 patients experienced improvement in clinical status; in no patient did an elevated prostate acid phosphatase return to normal. All patients entered on study have progressed and died: median time to progression was 94 days (6 to 625 days); median survival was 297 days (6-1152 days). The primary toxicity of carboplatin was myelosuppression. The median WBC and platelet nadirs after cycle one were 3150/cu mm and 93,000/cu mm, respectively. Dose escalations to grade 2 or greater myelosuppression were mandated. Twenty-six achieved at least grade 2 myelosuppression during carboplatin treatment. We conclude that carboplatin administered at this dose and schedule has no important activity in hormone refractory prostate cancer.
A total of 83 patients with metastatic transitional cell carcinoma who had previously received no systemic therapy entered a randomized phase II evaluation of carboplatin and cis-dichloro-transdihydroxy-bis-isopropylamine platinum IV (CHIP), administered respectively at 400 and 270 mg./m.2 every 28 days. Among evaluable patients with measurable disease response rates were 3 of 22 (14%, 95% confidence interval 5 to 35%) for carboplatin and 4 of 25 (16%, 95% confidence interval 5 to 36%) for CHIP. Among 17 patients with evaluable but not measurable metastases (10 carboplatin and 7 CHIP recipients) there were no responses. Median survival for 64 evaluable patients was 4.8 months (5.0 months for carboplatin and 4.3 months for CHIP recipients). Independent factors prognostic for survival (p less than 0.01) were performance status (0 or 1 versus 2 or 3), liver metastases, prior radiation therapy and recent weight loss (p = 0.02). Multivariate analysis confirmed that a performance status of 2 or 3 and liver metastases were predictive of shorter survival. A total of 31% of the patients treated with carboplatin and 34% of those who received CHIP experienced severe or life-threatening myelosuppression. While the response rates with carboplatin and CHIP are modest, we believe that the characteristics of these agents indicate that they should be evaluated further.
Hospital patients (n = 17) received 0.216 mmol/min kg body weight of ethanol as an intravenous infusion over 60 min. At fixed time intervals during and after administration, two consecutive samples of whole blood (5 ml each) were taken from a cubital vein. The plasma fraction was obtained by centrifugation of one of the tubes. The concentrations of ethanol in whole blood and plasma were determined by headspace gas chromatography and the water contents of the specimens by desiccation. The mean plasma:whole blood ratio of ethanol was 1.10:1, range 1.03:1 to 1.24:1 (n = 159). The components of variance (SD) within subjects and between subjects were 0.0293 (CV 2.7%) and 0.0165 (CV 1.5%) respectively. The 95% confidence interval ranged from 1.03:1 to 1.16:1 for a single new determination in a subject from the same population. The average water content in plasma and whole blood were 91.8% w/w (SD 0.49) and 80.1% w/w (SD 1.03) respectively. Neither the mean plasma:blood ratio of ethanol nor the water content of the specimens depended on sampling time after ethanol administration.
Previous studies suggest that severe symptoms of the 'TUR syndrome' occur from transurethral prostatic resection only when the volume of irrigant absorbed exceeds 2000 ml. An ethanol-containing irrigating fluid was used in this study of 100 transurethral resections so that the irrigant absorption could be monitored by measuring ethanol in expired air. Fluid absorption was found in 41 patients, and in nine of them the volume of irrigant absorbed exceeded 1000 ml. Four of these operations were terminated promptly when the ethanol monitoring indicated rapid massive absorption that threatened to exceed 2000 ml. There were few and only mild adverse effects of the irrigant by following this regimen. It is concluded that ethanol monitoring makes it possible to prevent the TUR syndrome by selective termination of those operations in which large amounts of irrigant is absorbed.
Signs and symptoms, circulatory changes and the diffusion of fluid and electrolytes were examined over 10-min periods in the course of 12 transurethral resections of the prostate (TURP) during which more than 1 litre of glycine solution was absorbed. Signs of the TURP syndrome were seen in 10 patients. During the first 20 min of absorption there was hypervolaemia, a marked diffusion of electrolytes from the interstitial space to the plasma, and elevation of central venous pressure. Patients who developed hypertension (n = 6) and chest pains (n = 3) had a smaller blood loss than those who did not. After 20 min of irrigant absorption there was an increased flow of fluid from the plasma to the interstitial space coupled with only a small diffusion of sodium. This promoted hypovolaemia and hypotension.
Transurethral resection of the prostate was performed using intermittent-flow bladder irrigation (n = 50), or by continuous-flow irrigation, using a suprapubic trocar (n = 50). The irrigant solution contained 1.5% glycine +1% ethanol and fluid absorption was measured from the ethanol content of the expired breath. Fluid absorption was significantly lower in patients receiving continuous-flow irrigation (p less than 0.007) although major absorption occurred in one of these patients. The immediate detection of absorption with the ethanol method allowed us to stop one of the operations performed with intermittent bladder irrigation, at which 2 l of fluid had been absorbed in 20 min. With correction for the amount of removed prostatic tissue, there were no differences in operation time or blood loss between the two types of irrigation.
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The initial 227 consecutive prenatal ultrasound examinations by two family physicians in an urban community health center were compared with actual birth outcomes. Of 186 examinations for which follow-up information was available, 162 infants were represented. The sampling rate was 81%. No serious anomalies were noted by ultrasound. One placenta previa, one fetal death, and two unsuspected cases of twins were detected by ultrasound. These data represent one of the first detailed reports of outcomes reflecting family physicians' psychomotor and cognitive skill in the use of obstetric ultrasound. The high accuracy (92% to 96%) of correct ultrasound dating suggests that a short postgraduate continuing medical education course was effective for these two family physicians. The accuracy rate compares favorably to more rigorous training. This structured format utilizing the average of four direct measurements for ultrasound-estimated gestational age and three anatomy ratios for assessing proper imaging relationships or growth symmetry may be useful as other family physicians develop educational methods and quality-assurance protocols in this area.