Search PubMed⌕ Search

Biomedical subjects

R G Hahn

Publications and source records attributed to R G Hahn.

At least 55 records · Page 3Linked to original sources

Distribution and elimination of the solute and water components of urological irrigating fluids.

OBJECTIVE: Irrigating fluids are used to dilate mucosal spaces and to remove blood and cut tissue from the operating field during endoscopic procedures. We have studied their disposition, since irrigating solutions are sometimes absorbed and may therefore be regarded as intravenous drugs. MATERIAL AND METHODS: The distribution and the rate of elimination of four irrigating fluids containing glycine, mannitol and sorbitol were studied after infusing 0.75 ml/kg/min of them over a period of 20 min in 10 male volunteers. Kinetic calculations were based on 12 blood samples collected over 120 min using traditional pharmacokinetics for the solutes and volume kinetics for the water component. RESULTS: The solutes had distribution half-lives of between 3 and 7 min; the elimination half-lives were 39 min (glycine), 97 min (mannitol) and 33 min (sorbitol). The volume of distribution during steady state was between 20 and 36 litres, while the volume of the body fluid space expanded by the water component of the irrigating fluids varied between 6 and 9 litres. Although the solutes became distributed over a much larger space than the infused fluid volume, the intersubject variation was smaller for the solute concentrations than for the dilution of the plasma fraction of the blood. CONCLUSIONS: The kinetics of the solute and water components of urological irrigating fluids can be analysed and compared using computer-based mathematical models.

Adult↗

The use of ethanol to monitor fluid absorption during transurethral resection of the prostate.

Ethanol monitoring is a method for assessing fluid absorption during transurethral resection of the prostate. The method is based on the principle that absorption can be measured by expired-breath tests provided that an irrigating fluid containing ethanol 1% is used. A nomogram for transformation of the ethanol data into meaningful indices of fluid absorption, such as the volume of irrigant absorbed and the degree of hyponatraemia, has been approved for routine use within the European Union. To make a correct interpretation, however, one must learn how to distinguish the pattern of breath ethanol changes typical of absorption of fluid directly into the blood from the pattern associated with the rare intraoperative events in which fluid is deposited in a pool in the retro- or intraperitoneal space. The ethanol method is well documented, but it is still sparsely used outside Scandinavia, due to its lack of a patent and differing opinions concerning the need for measuring fluid absorption.

Absorption↗

Glycine toxicity after high-dose i.v. infusion of 1.5% glycine in the mouse.

Glycine 1.5% is the most widely used irrigating fluid during endoscopic procedures. To investigate if glycine toxicity is a mechanism promoting a fatal outcome when the solution is absorbed, we administered glycine 200 or 300 ml kg-1 dissolved in sterile water or normal saline, and also normal saline alone, over 60 min by i.v. infusion to 100 mice under methoxyflurane anaesthesia. Survival rates were 29% after 1.5% glycine, 21% after 1.5% glycine in normal saline, 67% after normal saline and 100% in controls. Both solutions containing glycine induced bradycardia and prolongation of the PQ interval and QRS duration, while only 1.5% glycine increased the water content of the myocardium. These results suggest that glycine promotes bradycardia and death, regardless of whether hyponatraemia or hypo-osmolality is present. We conclude that glycine toxicity is an important factor that increases the risk of administration of an irrigating fluid.

Animals↗

Stability of the interstitial matrix after crystalloid fluid loading studied by volume kinetic analysis.

To investigate if fluid therapy changes the prerequisites for the development of oedema, four i.v. infusions of Ringer's solution 25 ml kg-1 were given over 15 or 30 min in a randomized crossover study to 10 healthy male volunteers, aged 28-40 (mean 31) yr. Blood haemoglobin concentration, measured every 5 min for 90 min, and urinary excretion were used as input data for volume kinetic analysis. The results showed that the elimination rate constant (kr) was higher when another infusion had been given earlier on the same day (208 vs 140 ml min-1; P < 0.002) and the size of V1 was larger during the 15-min infusions (4.7 vs 3.2 litre; P < 0.02). However, the size of V2 and the rate constant for the exchange of fluid between V1 and V2 were similar during all infusions. We conclude that a fluid challenge makes elimination of further infused fluid more effective but does not change compliance with volume expansion in healthy volunteers.

Adult↗

Volume kinetics of Ringer's solution in hypovolemic volunteers.

BACKGROUND: The amount of Ringer's solution needed to restore normal blood volumes is thought to be three to five times the volume of blood lost. This therapy can be optimized by using a kinetic model that takes accounts for the rates of distribution and elimination of the infused fluid. METHODS: The authors infused 25 ml/kg Ringer's acetate solution into 10 male volunteers who were 23 to 33 yr old (mean, 28 yr) when they were normovolemic and after 450 ml and 900 ml blood had been withdrawn. One-volume and two-volume kinetic models were fitted to the dilution of the total venous hemoglobin and plasma albumin concentrations. RESULTS: Withdrawal of blood resulted in a progressive upward shift of the dilution-time curves of both markers. The two-volume model was statistically justified in 56 of the 60 analyzed data sets. The hemoglobin changes indicated that the body fluid space expanded by the infused fluid had a mean total volume of 10.7 l(+/-0.9 SEM). The elimination rate constant (kr) decreased with the degree of hypovolemia and was 133 ml/min (22 ml/min [SEM]), 100 ml/min (39 ml/min [SEM]), and 34 ml/min (7 ml/min [SEM]), respectively (P < 0.01). Plasma albumin indicated a slightly larger body fluid space expanded by the infused fluid, but kr was less (P < 0.02). Hypovolemia reduced the systolic and diastolic blood pressures by approximately 10 mmHg (P < 0.05). CONCLUSIONS: The dilution of the blood and the retention of infused Ringer's solution in the body increases in the presence of hypovolemia, which can be attributed chiefly to a reduction of the elimination rate constant.

Adult↗

Early hemodynamic changes during uncontrolled intra-abdominal bleeding.

Central hemodynamics was studied in 32 pigs during the first 10 min after making a 5-mm laceration in the infrarenal aorta. Blood flow probes were placed proximally and distally to the site of the bleeding and also over the portal vein and renal artery. We found that the bleeding, which was indicated by a difference in the rate of blood flow between the two aortic probes, stopped spontaneously after about 3 min. The short-term changes in blood flow rates closely followed simple monoexponential functions with mean half-times of 34 (proximal aorta), approximately 10 (lower aorta), 27 (splanchnic) and 21 s (kidney) to reach steady-state levels amounting to 20, 20, 27 and 8% of the baseline flow rates, respectively.

Adaptation, Physiological↗

Volume kinetics of Ringer's solution and dextran 3% during induction of spinal anaesthesia for caesarean section.

PURPOSE: To study how the body handles fluid given intravenously during the onset of spinal anaesthesia in women scheduled for Caesarean section. METHODS: The effect of spinal anaesthesia on the volume kinetics of a constant-rate infusion of 25 ml.kg-1 of Ringer's solution (n = 11) and 10 ml.kg-1 of dextran 3% 60 (n = 8) was studied before elective Caesarean section. Measurements of the blood haemoglobin concentration and urine excretion served as input variables in calculations of the size(s) of the body fluid spaces expanded by the infused fluid. The blood glucose level was also monitored. RESULTS: When a one-volume kinetic model were fitted to the data, spinal anaesthesia reduced the size of the expanded body fluid space by 30% (Ringer's) and 58% (dextran) (P < 0.02) When a two-volume model was statistically justified, anaesthesia reduced the rate of fluid equilibration between the two expanded body fluid spaces by 47% and 19%, respectively (P < 0.04) The baseline volume for the primary (central) fluid space was smaller than the expected plasma volume; 1.5 l for Ringer's solution and 0.9 l for dextran. Only small changes in the blood glucose concentration were found. CONCLUSION: The onset of spinal anaesthesia induces acute changes in the body's handling of infused fluid that can be described by volume kinetic analysis.

Adult↗

Volume effect of Ringer's solution in the blood during general anaesthesia.

Ringer's solution expands blood volume by between 20% and 25% in awake volunteers, but little is known about its volume effect during general anaesthesia. In 35 men with a mean age of 70 years, the power of various intra-operative factors to change blood volume as estimated by the haemoglobin dilution method were analysed by multiple linear regression every 10 min during transurethral resection of the prostate performed under enflurane anaesthesia. The results show that blood volume increased by 60% of the infused Ringer's solution and by 35% of the irrigating fluid absorbed directly into the blood, while it decreased by slightly more than 100% of the bled volume. There was no correlation between systolic pressure and blood volume changes. This suggests that the volume effect of Ringer's solution in the blood is greater than generally believed during general anaesthesia.

Absorption↗

Urinary excretion as an input variable in volume kinetic analysis of Ringer's solution.

The disposition of fluid given by i.v. infusion can be studied by fitting one-volume and two-volume kinetic models to the fractioned dilution of blood haemoglobin and serum albumin concentrations over time. However, the two-volume model is sometimes associated with a high standard error in estimating the size of the secondary (peripheral) body fluid space, V2. To examine if a fixed elimination rate constant (kr) determined by urinary excretion can be used to make the model more stable, we infused Ringer's acetate 25 ml kg-1 over 30 min in 15 male volunteers (mean age 35 yr). A fixed kr increased the total residual error when curve-fitting was applied according to the one-volume model. The two-volume model was improved when there was a strong within-patient covariance between kr and V2 (r2 < or = -0.98). The size of V2 was 10 litre when the fixed and model-generated values of kr agreed fully.

Adult↗

Beta 2-adrenergic responsiveness in vivo during abdominal surgery.

We have studied adrenergic function in vivo during anaesthesia and surgery. Epinephrine 50 ng kg-1 min-1 was given by i.v. infusion over 30 min to 10 healthy adult volunteers and to 10 patients undergoing abdominal operations. The cAMP response to stimulation by epinephrine, which was obtained as the area under the curve (AUC) for plasma cAMP concentration divided by the AUC for plasma concentration of epinephrine, was more pronounced during surgery (mean ratio 3.5) than in the control situation (ratio 1.4; P < 0.02). This resulted in greater hypokalaemic and hyperglycaemic responses (ratios -0.67 and 4.5) than in the control group (ratios -0.33 and 1.6, respectively; P < 0.004). Mean arterial pressure decreased in the control group while it increased in the study group, and serum cortisol concentration was higher in those who underwent surgery (P < 0.02). These results are consistent with an increased adrenergic response during abdominal surgery.

Abdomen↗

Central and regional hemodynamics during crystalloid fluid therapy after uncontrolled intra-abdominal bleeding.

OBJECTIVE: To study the effect of graded crystalloid fluid resuscitation on central hemodynamics and outcome after intra-abdominal hemorrhage. METHODS: Ten minutes after a 5-mm long laceration was produced in the infrarenal aorta, 32 pigs were randomized to receive either no fluid or Ringer's solution in the proportion 1:1, 2:1, or 3:1 to the expected amount of blood lost per hour (26 mL kg[-1]) over 2 hours. The hemodynamics were studied using arterial and pulmonary artery catheters and four blood flow probes placed over major blood vessels. RESULTS: During the first 40 minutes after the injury, the respective blood flow rates in the distal aorta were 39% (no fluid), 41% (1:1), 56% (2:1), and 56% (3:1) of the baseline flow. Fluid resuscitation increased cardiac output but had no effect on arterial pressure, oxygen consumption, pH, or base excess. Rebleeding occurred only with the 2:1 and 3:1 fluid programs. Survival was highest with the 1:1 and 2:1 programs. CONCLUSIONS: Crystalloid fluid therapy improved the hemodynamic status but increased the risk of rebleeding. Therefore, a moderate fluid program offered the best chance of survival.

Animals↗

Central and regional hemodynamics during uncontrolled bleeding using hypertonic saline dextran for resuscitation.

The effects of hypertonic (7.5%) saline/6% dextran 70 (HSD) on central and regional hemodynamics were studied during uncontrolled intra-abdominal bleeding in 16 anesthetized pigs. Ultrasonic flow probes were placed proximally and distally to an aortic injury to indicate the incidence and extent of rebleeding after injecting 4 mL kg(-1) (N = 8) and 2.65 mL kg(-1) (N = 8) of HSD 10 min after the vascular injury was induced. The initial aortic bleeding reduced the blood flow rates to 71% of baseline in the skin, 53% in the splanchnic region, 42% in the upper aorta, and 15% in the kidney. Cardiac output dropped to 46% and the mean arterial pressure to 57% of baseline. The injection of HSD was followed by a prompt increase in all blood flow rates, but rebleeding started within 2 min in 13 of the pigs (81%). A second period of rebleeding occurred in six of them. The rebleeding averaged 300 mL, which is 62% of the blood lost when the aortic injury was induced. There was no significant difference between the treatment groups with respect to these blood losses or to the oxygen consumption, which was not restored by HSD. Five animals in each treatment group died after about 70 min, while the remaining six pigs (38%) survived the 120 min study period. These results suggest that HSD in the recommended dose, and even two-thirds thereof, promotes rebleeding when given shortly after a low energy intra-abdominal aortic injury. The fluid seems to have no beneficial effect on this type of uncontrolled hemorrhage.

Animals↗

Operative course of transurethral resection of the prostate and progression of prostate cancer.

Surgery has the potential to disseminate cancer cells, and we therefore hypothesized that extensive transurethral resections of the prostate (TURP) would be followed by a worse prognosis than minor ones. For this purpose, the association between the extent of surgery, disease progression, and mortality was studied in 138 patients with prostatic cancer who had undergone TURP. The results show that a large bleed (> or = 275 ml) indicated a slightly increased relative risk of general progression of the cancer (relative risk (RR) = 1.9, 95% confidence interval (CI) = 0.9-4.1) and death (RR = 1.5, CI = 0.6-3.3). Other parameters of extensive surgery, such as the operating time and fluid absorption, were not associated with increased risk. Patients with a medical disease, however, such as hypertension and congestive heart failure, had a significantly higher relative risk of general progression (RR = 2.7, CI = 1.2-6.1) and death from prostatic cancer (RR = 4.6, CI = 2.0-10.7) in addition to an increased relative risk of death from other causes (RR = 3.7, CI = 1.3-10.5). We conclude that concurrent medical disease, but not an extensive TURP, worsened the prognosis of patients with prostatic cancer who underwent TURP.

Adenocarcinoma↗

Double-blind randomized study of symptoms associated with absorption of glycine 1.5% or mannitol 3% during transurethral resection of the prostate.

PURPOSE: We studied which irrigating fluid, glycine 1.5% or mannitol 3%, is associated with the most favorable adverse effects profile when absorbed by the patient during transurethral resection of the prostate. MATERIALS AND METHODS: Irrigating fluid bags containing mannitol 3% or glycine 1.5%, both with added ethanol 1% as an indicator of fluid absorption, were used in a randomized double-blind fashion during 394 transurethral prostatic resections. The incidence of 13 symptoms was studied in 52 patients (13%) who absorbed more than 500 ml. fluid. RESULTS: The incidence of circulatory symptoms did not differ between the fluids but the risk of neurological symptoms, such as nausea, after transurethral prostatic resection was 4.8 times higher when glycine 1.5% was absorbed (p <0.04). An increase of 1,000 ml. in the volume of irrigant absorbed increased the overall risk for circulatory symptoms by a factor of 3.4 (p <0.03) and the risk of neurological symptoms by a factor of 4.4 (p <0.02). CONCLUSIONS: Absorption of mannitol 3% during transurethral prostatic resection is associated with fewer neurological symptoms than glycine 1.5%.

Absorption↗

Fluid absorption and the long-term outcome after transcervical resection of the endometrium.

BACKGROUND: Fluid absorption may cause symptoms of acute volume overload and has also been associated with a less favorable outcome after endometrial resection. To further study this topic, we evaluated the incidence of fluid absorption, the factors associated with absorption, and the relationship between fluid absorption and the long-term outcome after TCRE. METHOD: Two hunded and sixty-five women underwent TCRE in which the absorption of irrigating fluid (glycine 1.5%) was measured volumetrically. Physical examinations were made and questions about menstrual blood loss and cyclic pelvic pain were asked before the operation and 12 weeks and 1, 2, and 3 years later. RESULTS: Fluid absorption was increased in patients treated with a GnRH analogue (leuprolide acetate) prior to the TCRE (p<0.007) and also when a submucous myoma was removed during the operation (p<0.0001). About 40% of the women operated on still had menstrual bleeds 1 year later, and this correlated with a larger fluid absorption (p<0.04). Dysmenorrhea disappeared in half the patients, while 17% of those who were pain-free before the TCRE had developed cyclic pelvic pain at 1 year, an outcome also associated with a larger fluid absorption (p<0.02). Pain correlated with lower patient satisfaction, preserved menstrual bleeds, and with the presence of remnants of endometrial tissue as imaged by transvaginal ultrasonography. CONCLUSIONS: Resection of a submucous adenoma increases the risk of fluid absorption during TCRE. The results also indicate that fluid absorption is associated with persistent menstrual bleeding and late development of cyclic pelvic pain.

Absorption↗

Pharmacokinetics of ethanol in patients with renal failure before and after hemodialysis.

We studied the pharmacokinetics of ethanol in seven patients suffering from terminal renal failure before and after they underwent hemodialysis. Ethanol (0.40 g/kg) was administered in the morning after an overnight fast by a constant rate intravenous (i.v.) infusion over 45 min. After removing a mean fluid volume of 2.46 +/- 0.48 liters (+/- SD), span 1.76-3.43 liters by hemodialysis, the same subjects received a second i.v. infusion of ethanol after they had eaten lunch. At exactly timed intervals of 0, 45, 90, 105, 120, 135, 150, 165, and 180 min from the start of the infusion, two blood-samples were drawn and the plasma portion of one of them was obtained by centrifugation. The concentration of ethanol in blood and plasma was determined by headspace gas chromatography and the water-content of whole blood was determined from the change in weight after desiccation. Plasma always contained a higher concentration of ethanol than whole blood and the mean plasma/whole blood ratio in patients with renal failure was 1.07:1 (span 1.05-1.10). The rate of ethanol disappearance from blood (beta-slope) was faster (0.185 +/- 0.013 versus 0.157 +/- 0.022 g/l/h), the Co value was higher (0.79 +/- 0.08 versus 0.73 +/- 0.10 g/l) and the apparent volume of distribution (Vd) of ethanol was lower (0.507 +/- 0.049 versus 0.558 +/- 0.078 l/kg) after hemodialysis. The water content of whole blood was significantly higher (P < 0.001) before dialysis (88.6 +/- 1.97 g/100 ml) compared with after dialysis (87.4 +/- 2.01 g/100 ml). The higher Vd for ethanol and lower Co as well as higher blood-water content are to be expected for a over hydrated condition before hemodialysis. The swifter rate of ethanol elimination from blood (beta-slope) after hemodialysis should be interpreted with caution because eating a meal before the second infusion of ethanol is a confounding factor. Nevertheless, the rate of elimination of ethanol from blood in patients with renal failure agreed reasonably well with values expected for healthy subjects, namely mean 0.15 g/l/h spanning from 0.10 to 0.20 g/l/h.

Central Nervous System Depressants↗