Predictors of Hypotension after Adrenalectomy for Pheochromocytoma.

The management of blood pressure is a significant concern for surgeons and anesthesiologists performing adrenalectomy for pheochromocytoma. We evaluated clinical factors in pheochromocytoma patients to identify the predictors of postoperative hypotension. The medical records of patients who underwent adrenalectomy for pheochromocytoma between 2001 and 2017 were retrospectively reviewed and clinical and biochemical data were evaluated. Of 29 patients, 13 patients needed catecholamine support in the perisurgical period while 16 patients did not. There were significant differences in median age, tumor size, and blood pressure drop (maxmin) between the 2 groups (68 vs 53 years old, p=0.045; 50 vs 32 mm diameter, p=0.022; 110 vs 71 mmHg, p=0.015 respectively). In univariate logistic analysis, age > 65.5 years, tumor size > 34.5 mm, urine metanephrine > 0.205 mg/day and urine normetanephrine > 0.665 mg/day were significant predictors of prolonged hypotension requiring postoperative catecholamine support. Tumor size and urine metanephrine and urine normetanephrine levels were correlated with postoperative hypotension. These predictors may help in the safe perioperative management of pheochromocytoma patients treated with adrenalectomy.

Minute-to-minute urine flow rate variability: a retrospective survey of its ability to provide early warning of acute hypotension in critically ill multiple trauma patients.

PURPOSE: Dynamic changes in urine output and neurological status are the recognized clinical signs of hemodynamically significant hemorrhage. In the present study, we analyzed the dynamic minute-to-minute changes in the UFR and also the changes in its minute-to-minute variability in a group of critically ill multiple trauma patients whose blood pressures were normal on admission to the ICU but who subsequently developed hypotension within the first few hours of their ICU admission. PATIENTS AND METHODS: The study was retrospective and observational. Demographic and clinical data were extracted from the computerized register information systems initially; the clinical and laboratory data of 100 critically ill patients with multiple trauma who were admitted to the ICU during the study period were analyzed. Of this group, ten patients were eventually included in the study on the basis of the inclusion criteria. RESULTS: The minute-to-minute urine flow rate (UFR) and urine flow rate variability (UFRV) both decreased significantly during the periods of hypotension (p values 0.001 and 0.006, respectively). Notably, the decrease in UFRV preceded by at least 30 min a corresponding decline in the systolic and mean arterial blood pressures, which manifested as a flattening of UFRV amplitude which was observed prior to the occurrence of the lowest recorded systolic and mean arterial blood pressures. Statistical analysis by the Pearson method demonstrated a strong direct correlation between the decrease in UFRV and the decrease in the MAP (R = 0.9, p = 0.001), and SBP (R = 0.86, p = 0.001) and the decreasing urine output per hour (R = 0.88, p < 0.001). CONCLUSION: We found that changes in UFRV correlate strongly with systolic and mean arterial blood pressures. We feel that this parameter could potentially serve as an early signal of hemodynamic deterioration due to occult bleeding in critically ill trauma patients, and might also be able to identify the optimal end-point of hemodynamic resuscitative measures in these patients.

Increase in urinary sodium excretion in spinal cord injury patients in the emergency department.

OBJECTIVE: Spinal cord injury (SCI) is a pathological condition known to produce hyponatremia. The aim of this study was to elucidate the dynamics of urinary sodium excretion in patients with spinal cord injury. METHODS: SCI patients undergoing intensive care management were enrolled in this study. These patients were divided into two groups: those with Frankel Grade A spinal cord injury manifesting complete, severe motor disorders (FA group) and those with incomplete spinal cord injury (non-FA group). The occurrence of episode of hyponatremia (serum sodium <135 mmol/L), hypotension, and bradycardia during the first 14 hospital days was counted and fractional excretion of sodium (FENa) was calculated on the 1st, 7th, and 14th hospital days. RESULTS: Thirty-four patients (FA group, n = 9; non-FA group, n = 25) were included. Eight patients (88.9 %) in the FA group and three patients (12 %) in the non-FA group experienced at least one episode of hyponatremia during the first 14 hospital days. In the FA group, the FENa was significantly increased on the 7th and 14th hospital days compared to the 1st hospital day. FENa on the 14th hospital day was a significant independent predictor of hyponatremic episodes. Hypotension and bradycardia as the symptoms of sympathetic blockade differed significantly as independent predictors of increased FENa on the 14th hospital day. CONCLUSION: Urinary sodium excretion calculated by FENa increased in patients with severe spinal cord injury. Sympathetic blockade due to SCI may increase urine sodium excretion and lead to hyponatremia.

High pre-operative urinary norepinephrine is an independent determinant of peri-operative hemodynamic instability in unilateral pheochromocytoma/paraganglioma removal.

BACKGROUND: Peri-operative hemodynamic instability (HDI) may increase peri-operative morbidity in pheochromocytoma/paraganglioma (PPGL) patients. OBJECTIVE: This study aimed to determine which tumor-related risk factors could lead to peri-operative HDI in unilateral or single PPGL removal. METHODS: Before surgery, 66 PPGL patients had at least two sets of 24 h urine collected for fractionated catecholamine analysis. At surgery, an arterial line was inserted to record systolic blood pressure (SBP), diastolic BP, and mean arterial BP (MAP). Peri-operative HDI was defined as hypertension (SBP > 160 mmHg) and/or hypotension (SBP < 90 mmHg and/or MAP < 60 mmHg) for >10 consecutive minutes either intra-operatively or within the first 12 h after surgery. Urinary fractionated catecholamines and other variables were compared between those with peri-operative HDI (group I) and those without (group II). RESULTS: A total of 15 (22.7 %) patients belonged to group I, while 51 patients belonged to group II. One (1.5 %) patient died 9 days after surgery. Relative to group II, group I had significantly higher urinary norepinephrine (NE) (5,488.0 vs. 1,980.0 nmol/L, p < 0.001), urinary normetanephrine (5,130.9 vs. 3,853.4 nmol/L, p = 0.045), maximum SBP at operation (188.2 vs. 167.4 mmHg, p = 0.037), but lower MAP after operation (78.9 vs. 91.8 mmHg, p = 0.026). Urinary NE (OD 1.02, 95 % confidence interval [CI] 1.01-1.03, p = 0.046) was an independent risk factor for peri-operative HDI. The urinary NE level significantly correlated with maximum intra-operative SBP and MAP (r 0.692, p < 0.001; and r 0.669, p < 0.001, respectively) and inversely correlated with maximum post-operative MAP (r -0.305, p = 0.040). CONCLUSIONS: High pre-operative urinary NE was an independent tumor-related factor for peri-operative HDI and significantly correlated with sustained intra-operative hypertension and post-operative hypotension.

Physiological function of the angiotensin AT1a receptor in bone remodeling.

In order to determine whether the renin-angiotensin system (RAS) has any physiologic function in bone metabolism, mice lacking the gene encoding the major angiotensin II receptor isoform, AT1a, were studied using micro CT scanning, histomorphometric, and biochemical techniques. Three-dimensional (3D) micro CT analysis of the tibial metaphysis revealed that both male and female AT1a knockout mice exhibited an increased trabecular bone volume along with increased trabecular number and connectivity. Histomorphometric analysis of the tibial metaphysis indicated that the parameters of bone formation as well as resorption were increased, which was also supported by elevated serum osteocalcin and carboxy-terminal collagen crosslink (CTX) concentrations in the AT1a-deficient mice. Osteoclastogenesis and osteoblastogenesis assays in ex vivo cultures, however, did not reveal any intrinsic alterations in the differentiation potential of AT1a-deficient cells. Quantitative RT-PCR using RNA isolated from the tibia and femur revealed that the receptor activator of NF-κB ligand (RANKL)/osteoprotegerin (OPG) ratio and the expression of stromal cell-derived factor (SDF)1α were increased, whereas that of SOST was decreased in AT1a-deficient bone, which may account for the increased bone resorption and formation, respectively. AT1a-deficient mice also displayed a lean phenotype with reduced serum leptin levels. They maintained high bone mass with advancing age, and were protected from bone loss induced by ovariectomy. Collectively, the data suggest that RAS has a physiologic function in bone remodeling, and that signaling through AT1a negatively regulates bone turnover and bone mass.

Assessing cortisol production in preterm infants: do not dispose of the nappies.

The aim of this study was to develop a practical approach allowing a reliable and noninvasive assessment of cortisol production rates in premature infants. To measure daily urinary excretion rates of glucocorticoids, we developed a procedure using a hydraulic compression method to collect urine from cellulose nappies (diapers). Glucocorticoid metabolites were profiled by quantitative gas chromatography-mass spectrometry. Recovery of steroids after the process of hydraulic extraction from the nappy was approximately 100%. Consecutively, urinary excretion rates of glucocorticoids could be determined in nine healthy preterm infants. The median urinary excretion rate of glucocorticoids increased significantly during the first 5 d of life and remained between 566 microg/kg/d at d 5 and 302 microg/kg/d at 4 wk of age. However, this increase of urinary excretion rates of glucocorticoids in the first days of life was no longer significant when corrected for creatinine excretion. When calculated per square meter body surface area, the median urinary excretion rates of glucocorticoids were 5.1, 4.2, 4.1, and 3.7 mg/m2/d on d 5, and at wk, 2, 3, and 4, respectively. Urinary excretion rates of glucocorticoids constitute approximately 70% of the natural cortisol production rate as determined by stable isotope dilution technique in older children. Additionally, low cortisol production was detected in two of five preterm infants with arterial hypotension requiring treatment with catecholamines. In conclusion, 24-h urine collection using disposable nappies in combination with gas chromatography-mass spectrometry steroid profiling proved to be a reliable, noninvasive, nonstressful procedure to assess cortisol production and metabolism in premature infants.

Elevated dietary salt suppresses renin secretion but not thirst evoked by arterial hypotension in rats.

Increased dietary salt intake was used as a nonpharmacological tool to blunt hypotension-induced increases in plasma renin activity (PRA) in order to evaluate the contribution of the renin-angiotensin system (RAS) to hypotension-induced thirst. Rats were maintained on 8% NaCl (high) or 1% NaCl (standard) diet for at least 2 wk, and then arterial hypotension was produced by administration of the arteriolar vasodilator diazoxide. Despite marked reductions in PRA, rats maintained on the high-salt diet drank similar amounts of water, displayed similar latencies to drink, and had similar degrees of hypotension compared with rats maintained on the standard diet. Furthermore, blockade of ANG II production by an intravenous infusion of the angiotensin-converting enzyme inhibitor captopril attenuated the hypotension-induced water intake similarly in rats fed standard and high-salt diet. Additional experiments showed that increases in dietary salt did not alter thirst stimulated by the acetylcholine agonist carbachol administered into the lateral ventricle; however, increases in dietary salt did enhance thirst evoked by central ANG II. Collectively, the present findings suggest that hypotension-evoked thirst in rats fed a high-salt diet is dependent on the peripheral RAS despite marked reductions in PRA.

Gravimetric method for the dynamic measurement of urine flow.

The rate of urine formation is a primary index of renal function, but no techniques are currently available to accurately measure low rates of urine flow on a continuous basis, such as are normally found in rats. We developed a gravimetric method for the dynamic measurement of urine flow in anesthetized rats. Catheters were inserted directly into the ureters close to the renal pelves, and a siphon was created to collect all of the urine formed as rapidly as it was produced. Urine flow was determined by measuring the weight of the urine using a direct-reading analytical balance interfaced to a computer. Basal urine flow was measured at 2-sec intervals for 30 to 60 min. The dynamic response of urine flow to a rapid decrease in arterial pressure produced by a bolus intravenous injection of acetylcholine (0.5 micrograms) was also measured. Intrinsic drift, evaporative losses, and the responsiveness of the system to several fixed pump flows in the low physiologic range were evaluated in vitro. The gravimetric method described was able to continuously measure basal urine flows that averaged 37.3 +/- 12.4 microliters/min. Error due to drift and evaporation was negligible, totaling less than 1% of the measured urine flow. Acetylcholine-induced declines in arterial pressure were followed within 8 sec by a decline in urine flow. These data demonstrate that this new gravimetric method provides a simple, inexpensive, dynamic measurement of urine flow in the microliter/min range.

Prehospital hypertonic saline/dextran infusion for post-traumatic hypotension. The U.S.A. Multicenter Trial.

The safety and efficacy of 7.5% sodium chloride in 6% dextran 70 (HSD) in posttraumatic hypotension was evaluated in Houston, Denver, and Milwaukee. Multicentered, blinded, prospective randomized studies were developed comparing 250 mL of HSD versus 250 mL of normal crystalloid solution administered before routine prehospital and emergency center resuscitation. During a 13-month period, 422 patients were enrolled, 211 of whom subsequently underwent operative procedures. Three hundred fifty-nine patients met criteria for efficacy analysis, 51% of whom were in the HSD group. Seventy-two per cent of all patients were victims of penetrating trauma. The mean injury severity score (19), Trauma Score plus Injury Severity Score (TRISS) probability of survival, revised trauma scores (5.9), age, ambulance times, preinfusion blood pressure, and etiology distribution were identical between groups. The total amount of fluid administered, white blood cell count, arterial blood gases, potassium, or bicarbonate also were identical between groups. The HSD group had an improved blood pressure (p = 0.024). Hematocrit, sodium chloride, and osmolality levels were significantly elevated in the Emergency Center. Although no difference in overall survival was demonstrated, the HSD group requiring surgery did have a better survival (p = 0.02), with some variance among centers. The HSD group had fewer complications that the standard treatment group (7 versus 24). A greater incidence of adult respiratory distress syndrome, renal failure, and coagulopathy occurred in the standard treatment group. No anaphylactoid nor Dextran-related coagulopathies occurred in the HSD group. Although this trial demonstrated trends supportive of HSD in hypotensive hemorrhagic shock patients requiring surgery, a larger sample size will be required to establish which subgroups of trauma patients might maximally benefit from the prehospital use of a small volume of hyperosmolar solution. This study demonstrates the safety of administering 250 mL 7.5% HDS to this group of patients.

Relation of renal thromboxane A2 production to urine flow, electrolyte excretion and plasma renin activity in control state and drug induced hypotension.

The functional importance of renal TxB2 generation in the maintenance of elevated arterial blood pressure in essential hypertension was followed in 22 patients, using the method of sustained blood pressure decrease by i.v. sodium nitroprusside infusion. Linear correlation between urinary excretion of TxB2, urine flow, and sodium excretion could be established in both control and hypotensive periods. Presumably, changes in urinary excretion of TxB2 reflect a secondary intrarenal counterregulatory response.

Isovolemic hypotension in ovine fetus: plasma arginine vasopressin response and urinary effects.

Chronically prepared third trimester fetal lambs were administered intravenous infusions of nitropruside. Mean basal systolic and diastolic blood pressure (59.8 and 42.4 mmHg, respectively) decreased significantly during the infusion (49.2 and 36.8 mmHg, respectively) and increased significantly during the recovery period (66.4 and 48.5 mmHg, respectively). Fetal plasma arginine vasopressin (AVP) significantly increased from a mean basal level of 1.25 +/- 0.09 to 6.81 +/- 0.39 pg/ml during the hypotensive period. Urinary AVP basal levels of 1.21 +/- 0.13 pg/ml increased to 3.18 +/- 0.66 pg/ml during the hypotensive period and 5.87 +/- 0.82 pg/ml during the recovery period (P less than 0.05). The fetal urinary response to nitroprusside appeared biphasic. The hypotensive phase was marked by decreases in both free water and osmolar clearances. During the recovery phase free water clearance remained decreased, while osmolar clearance returned to basal levels. Thus AVP secretion represents an important mechanism for ovine fetal modulation of solute and water excretion in response to utero hypotensive stress.

Urinary prostaglandins in the Lyon strains of hypertensive, normotensive, and low blood pressure rats.

A longitudinal study of the urinary excretion of prostaglandins (PGs) E and F alpha was performed in simultaneously selected hypertensive (LH), normotensive (LN), and low blood pressure (LL) female rats of the Lyon strains aged from 5 to 45 weeks. The urinary excretion of PGE did not significantly differ between LL and LN rats whereas in LH rats it was found to be significantly lower than that of LN or LL rats starting at the age of 32 weeks. The urinary excretion of PGF alpha was significantly reduced in both LL and LH rats; however, this decrease was more marked in LH than in LL animals and, from 9 weeks of age, the urinary PGF alpha were significantly lower in LH than in age-matched LL rats. In addition, both PGE and PGF alpha were found to be significantly and negatively related to the systolic blood pressure level in LH rate (r = -0.56, n = 58, p less than 0.001 for PGE; and r = -0.78, n = 58, p less than 0.001 for PGF alpha) but not in LN of LL animals. In conclusion, it seems unlikely that renal PGs could play a primary role in the spontaneous hypertension observed in the Lyon strain of rats.

[Functional state of the cortical and medullary layers of the adrenals in primary arterial hypotension]. / Funktsional'noe sostoinaie korkovogo i mozgovogo sloev nadpochechnikov pri pervichnoi arterial'noi gipotonii.

The functional state of the cortical and medullar layers of the adrenal glands was studied in 127 patients with primary arterial hypotension (109 females and 18 males, aged 17 to 48 years). As shown by daily urine excretion, hypotonic patients had a decreased basal activity of the glucocorticoid and androgenic function of the adrenal cortex in comparison with those in normal individuals. The potential of the adrenal cortex was preserved in these patients within sufficient limits. The adrenocorticotrophic function of the anterior lobe of the pituitary gland was found to decrease. Against the background of a reduction of the total excretion of all fractions a relative delay was noted in the process of glucocorticoids transformation into their precursors, as well as a relative predominance of glucocorticoids over mineralcorticoids, the content of desoxycorticosterone being reduced especially low. The content of adrenalin, noradrenaline and dophamine was below the normal level, the decrease being statistically significant. At the same time the excretion of DOPA was normal, on the average, the whole group of patients. The changes in the daily urine excretion of catecholamines and DOPA, as well as in their ratio indicate that the activity of both links of the sympathodrenal system is reduced in primary arterial hypotension.