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Background Bleeding during functional endoscopic sinus surgery is a challenge for the quality of the surgical field for surgeons. This study aimed to evaluate the effect of desmopressin premedication on blood loss and the quality of the surgical field in endoscopic sinus surgery. Methods A total of 90 American Society of Anesthesiologists physical status I–II patients underwent endoscopic sinus surgery for chronic sinusitis. They were randomly allocated to receive either desmopressin 0.3 μg/kg or saline before the operation. Management of anesthesia was achieved with propofol and remifentanil infusions, with moderate, controlled hypotension. Blood loss and quality of the surgical field were assessed after surgery. Effects of desmopressin on anesthetic requirements and hemodynamic variables were analyzed. Results Blood loss was significantly less in the desmopressin group (mean ± SD, 42 ± 8.7 ml) than in the control group (70 ± 9.2 ml, P  < 0.001). Surgeons were more satisfied with the surgical field in the desmopressin group than in the control group (median score, 4 [3–5] vs. 7 [6–9], P  < 0.001). Requirements for remifentanil and esmolol were lower in the desmopressin group than in the control group. Conclusions Premedication with desmopressin 0.3 μg/kg can effectively reduce bleeding during endoscopic sinus surgery.

Background Mild hypothermia (34–35 °C) increases perioperative blood loss. Our previous studies showed that desmopressin could have in vitro beneficial effects on hypothermia-induced primary haemostasis impairment. In this study, we investigate the in vitro effects of desmopressin on hypothermia-induced primary haemostasis impairment under the influence of aspirin in healthy volunteers. Methods Sixty healthy volunteers were randomly allocated to taking aspirin 100 mg or placebo for three days. On the sixth day blood samples were taken before and after the injection of desmopressin (1.5 microgram or 5 microgram) or normal saline subcutaneously. Measurements including Platelet Function Analyzer (PFA-100®) closure times, plasma von Willebrand Factor antigen, haemoglobin and platelet levels were made at 32 °C and 37 °C respectively. Results Collagen/epinephrine closure time (EPICT) was significantly prolonged by 21.13 % (95 %CI 2.34–39.74 %, p  = 0.021) in aspirin group at 37 °C. While hypothermia alone prolonged both collagen/adenosine diphosphate (ADPCT) and EPICT by 17.63 % (95 %CI 13.5–20.85 %, p  < 0.001) and 8.0 % (95 %CI 6.38–10.04 %, p  = 0.024) respectively, addition of aspirin only further prolonged EPICT by 19.9 % (95 %CI 3.32–36.49 %, p  = 0.013). In aspirin group, desmopressin 1.5 microgram and 5 microgram significantly reduced ADPCT to below baseline levels at 37 °C ( p  = 0.025 and <0.001 respectively), whereas reduction in EPICT was seen with desmopressin 5 microgram ( p =0.008). The effect was less pronounced at 32 °C, with a significant reduction in EPICT obtained with a dosage of 5 microgram only ( p  = 0.011). Conclusion It was shown that aspirin could further potentiate the hypothermia-induced closure time prolongations. Low dose desmopressin (1.5 microgram) reduced PFA-100® closure times towards baseline. A higher dosage (5 microgram) further reduced the closure times below baseline. Therefore low dose desmopressin (1.5 microgram) might have the potential to correct hypothermia-induced primary haemostasis impairment under the influence of aspirin during the perioperative period. Trial registration ClinicalTrials.gov: NCT01382134

To investigate (1) the pharmacokinetic and pharmacodynamic profiles of desmopressin in men from an age group with a high incidence of nocturia; and (2) circadian variation in the pharmacokinetic parameters. The study had an open, randomised, four-way cross-over design. Desmopressin was administered orally (0.2 mg) and intravenously (2 microg), daytime and night-time, yielding four in-hospital sessions, separated by at least 2 days. Blood samples were taken before and at predetermined time points up to 12 h after dosing. Pharmacokinetic parameters were derived using a two-compartmental model except for AUC(0-->t), which was derived using non-compartmental analysis. Bioavailability was estimated using AUC(0-->t) for the oral and the intravenous periods. Urine, for measurements of volume and osmolality, was collected in predetermined intervals before and until 12 h after dosing. Fifteen healthy men aged 55-70 years were included in the analysis. The concentration-time curve after 2 microg intravenous desmopressin was best described using a biexponential term. The mean (95% CI) AUC at night was 302 (272-335) pg x h/ml and in the day was 281 (253-312) pg x h/ml. No statistically significant differences were detected between night and day except for terminal half-life, which was 3.1 h at night and 2.8 h in the daytime (P=0.02). After oral desmopressin, concentrations above the limit of quantification (2.5 pg/ml) were only detected in 51% of the samples. Peak plasma concentration (Cmax) was 6.2 (5.1-7.5) pg/ml at night and 6.6 (5.5-7.9) pg/ml in the daytime. Median time to reach Cmax (tmax) was 1.5 (range 1.0-4.1) h at night and 1.5 (range 0.5-3.0) h in the day. The bioavailability was 0.08%. The pharmacodynamic effects of oral and intravenous desmopressin given in the daytime were similar during the first 6 h after dosing. The night-time dosing and daytime intravenous dose resulted in antidiuresis throughout the measuring period, while the effect of the daytime peroral dose receded after 6 h. The pharmacokinetic profile of desmopressin is biexponential. Terminal half-life was longer at night than in the daytime, but the difference is considered too small to be of clinical importance. The plasma levels given by the intravenous dose resulted in a duration of action of 12 h or more. Despite low bioavailability, the pharmacodynamic effects of oral desmopressin were similar in magnitude to those after intravenous dose at night and during the first 6 h after daytime administration.

Alterations of cell volume induced by changes of extracellular osmolality have been reported to regulate intracellular metabolic pathways. Hypo-osmotic cell swelling counteracts proteolysis and glycogen breakdown in the liver, whereas hyperosmotic cell shrinkage promotes protein breakdown, glycolysis and glycogenolysis. To investigate the effect of acute changes of extracellular osmolality on whole-body protein, glucose and lipid metabolism in vivo , we studied 10 male subjects during three conditions: (i) hyperosmolality was induced by fluid restriction and intravenous infusion of hypertonic NaCl (2–5%, wt/vol) during 17 h; (ii) hypo-osmolality was produced by intravenous administration of desmopressin, liberal water drinking and infusion of hypotonic saline (0.4%); and (iii) the iso-osmolality study comprised oral water intake ad libitum . Plasma osmolality increased from 285±1 to 296±1 mosm/kg ( P <0.001during hyperosmolality, and decreased from 286±1 to 265±1 mosm/kg during hypo-osmolality ( P <0.001). Total body leucine flux ([1- 13 C]leucine infusion technique), reflecting whole-body protein breakdown, as well as whole-body leucine oxidation rate (irreversible loss of amino acids) decreased significantly during hypo-osmolality. The glucose metabolic clearance rate during hyperinsulinaemic–euglycemic clamping increased significantly less during hypo-osmolality than iso-osmolality, indicating diminished peripheral insulin sensitivity. Glycerol turnover (2-[ 13 C]glycerol infusion technique), reflecting whole-body lipolysis, increased significantly during hypo-osmolar conditions. The results demonstrate that the metabolic adaptation to acute hypo-osmolality resembles that of acute fasting, that is, it results in protein sparing associated with increased lipolysis, ketogenesis and lipid oxidation and impaired insulin sensitivity of glucose metabolism.

Background Serum copeptin (sCoP) is used as a surrogate for plasma arginine vasopressin (pAVP) measurement in humans. Objective To measure pAVP and sCoP at rest and after osmotic‐ and non‐osmotic stimulation testing in dogs. Animals Eight young castrated/spayed healthy research Beagles, eight young intact dogs, and eight old neutered healthy client‐owned dogs. Methods In this prospective longitudinal study, pAVP and sCoP were measured under iso‐(baseline), hypo‐(water load followed by intravenous administration of desmopressin [WLT]), and hyper‐(water deprivation test [WDT]) osmolar conditions assessed by measured plasma osmolality (pOsm(m)), and after administration of arginine (AST), IV, and Bovril (BST), PO. The fraction of change (F) in a variable y (e.g., pAVP) between baseline (T0) and a timepoint X (TX) during testing was defined as Fy = [y (TX) – y (T0)]/y (T0). Results Baseline sCoP had wide inter‐individual variations. Mean [range] FpAVP and FsCoP at the end of WDT were +110% [+80; +142] and +18% [+0.4; +38] compared to baseline, respectively. Mean [range] FpAVP after water load and FsCoP after water load followed by desmopressin administration were −22% [−48; −0.5] and −29% [−39; −14] compared to baseline, respectively. Both FpAVP and FsCoP were strongly correlated to FpOsm(m) (r = +0.76, p = 0.004; r = +0.78, p = 0.002; respectively). When sCoP was measured at T4h instead of T2h during WLT, to reflect its longer half‐life reported in humans, the correlation between FpAVPP800 and FsCoP became excellent (r = +0.90, p < 0.001). No stimulation of sCoP secretion occurred during AST or BST. Conclusion and Clinical Importance Serum CoP could be used as a surrogate for pAVP measurement in healthy dogs.

Apelin and arginine-vasopressin (AVP) are conversely regulated by osmotic stimuli. We therefore hypothesized that activating the apelin receptor (apelin-R) with LIT01-196, a metabolically stable apelin-17 analog, may be beneficial for treating the Syndrome of Inappropriate Antidiuresis, in which AVP hypersecretion leads to hyponatremia. We show that LIT01-196, which behaves as a potent full agonist for the apelin-R, has an in vivo half-life of 156 minutes in the bloodstream after subcutaneous administration in control rats. In collecting ducts, LIT01-196 decreases dDAVP-induced cAMP production and apical cell surface expression of phosphorylated aquaporin 2 via AVP type 2 receptors, leading to an increase in aqueous diuresis. In a rat experimental model of AVP-induced hyponatremia, LIT01-196 subcutaneously administered blocks the antidiuretic effect of AVP and the AVP-induced increase in urinary osmolality and induces a progressive improvement of hyponatremia. Our data suggest that apelin-R activation constitutes an original approach for hyponatremia treatment. Apelin and AVP have opposing effects water balance in humans and rodents. Here, the authors report that a metabolically stable apelin-17 analog, by acting at the kidney level, reduces AVP-induced antidiuresis and improves hyponatremia in rodents, demonstrating a potential approach for treating water metabolism disorders.

Background Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have diverse effects on sodium and water homeostasis. They decrease thirst perception, potentially inhibit arginine vasopressin (AVP) production, and induce natriuresis. We present three cases of AVP deficiency (AVP-D) where GLP-1 RA initiation led to desmopressin dose reduction. Cases Three patients with AVP-D on stable desmopressin therapy started GLP-1 RAs for type 2 diabetes mellitus or obesity. Following weight loss and decreased thirst, all patients reduced their desmopressin dose while maintaining normal thirst and urine output. Discussion GLP-1 RAs influence sodium and water homeostasis through various mechanisms. In individuals with intact AVP systems, GLP-1 RAs may directly suppress AVP production and induce natriuresis in the kidney leading to increased water excretion. In AVP-D, with exogenous desmopressin replacing endogenous AVP, the osmotic permeability of collecting ducts is primarily influenced by desmopressin dose. Thus, increased distal fluid delivery may allow for lower desmopressin doses to maintain water balance. Conclusion Our findings indicate a potential interaction between GLP-1 RAs and desmopressin in AVP-D. Clinicians should reassess desmopressin dosage upon initiating GLP-1 RA therapy.

In a prospective study, 254 of 5649 unselected patients scheduled for surgery at our hospital were identified preoperatively as having either acquired (n=182) or inherited (n=72) impaired primary hemostasis (platelet dysfunction including von Willebrand disease). All patients were initially pretreated with desmopressin (DDAVP). Response to DDAVP or subsequent treatment(s) was defined as correction of any one of the abnormal PFA-100 platelet function tests. The non-responders were additionally treated with tranexamic acid or aprotinin; those with von Willebrand disease (vWD) received factor VIII concentrates with von Willebrand factor (vWF). Those still unresponsive to therapy received conjugated estrogens and, as a last attempt, a platelet transfusion. The administration of DDAVP led to a correction of platelet dysfunction in 229 of the 254 patients treated (90.2%). Tranexamic acid was effective in 12 of 16, aprotinin in 3 of 5, and factor VIII concentrates with vWF in all 4 patients with unresponsive to DDAVP. The remaining 6 patients were pretreated with conjugated estrogens, and 2 of these patients were additionally treated with platelet transfusion. The frequency of blood transfusion was lower, but not statistically significant (9.4% vs. 12.2%: p = 0.202) in preoperatively treated patients with impaired hemostasis than in patients without impaired hemostasis. In a retrospective group, the frequency of blood transfusion was statistically significant higher (89.3% vs. 11.3%: p < 0.001) in patients without preoperative correction of impaired hemostasis than in patients without impaired hemostasis. Preoperative correction of impaired primary hemostasis is possible in nearly all patients affected, and results in a reduction of homologous blood transfusions.

Arginine–vasopressin (AVP), a cyclic peptide hormone composed of nine amino acids, regulates water reabsorption by increasing intracellular cyclic adenosine monophosphate (cAMP) concentrations via the vasopressin V2 receptor (V2R). Plasma AVP is a valuable biomarker for the diagnosis of central diabetes insipidus (CDI) and is commonly measured using radioimmunoassay (RIA). However, RIA has several drawbacks, including a long hands-on time, complex procedures, and handling of radioisotopes with special equipment and facilities. In this study, we developed a bioassay to measure plasma AVP levels using HEK293 cells expressing an engineered V2R and a cAMP biosensor. To achieve high sensitivity, we screened V2R orthologs from 11 various mammalian species and found that the platypus V2R (pV2R) responded to AVP with approximately six-fold higher sensitivity than that observed by the human V2R. Furthermore, to reduce cross-reactivity with desmopressin (DDAVP), a V2R agonist used for CDI treatment, we introduced a previously described point mutation into pV2R, yielding an approximately 20-fold reduction of responsiveness to DDAVP while maintaining responsiveness to AVP. Finally, a comparison of plasma samples from 12 healthy individuals demonstrated a strong correlation (Pearson's correlation value: 0.90) between our bioassay and RIA. Overall, our assay offers a more rapid and convenient method for quantifying plasma AVP concentrations than existing techniques.

Rationale Hypothalamic–pituitary–adrenal axis dysregulation predicts poor clinical and biochemical response to antidepressants. Antiglucocorticoids have therapeutic benefits but most have a troublesome adverse event profile. Aspects of neuropsychological performance, notably working memory, are susceptible to corticosteroid modulation and are impaired in depression. Aspirin has been shown to attenuate the adrenocorticotropic hormone (ACTH) and cortisol response to physiological challenge suggesting its potential to act as an augmenting agent in depression. Objectives To examine the effect of sub-acute (300 mg daily for 7 days) aspirin pre-treatment on the cortisol awakening response and the effect of acute (600 mg) and sub-acute aspirin on the neuroendocrine and neuropsychological response to the arginine vasopressin analogue, desmopressin. Results We demonstrated that aspirin pre-treatment did not attenuate the cortisol or ACTH response to desmopressin but, as hypothesised, significantly reduced the cortisol awakening response and improved working memory. Conclusions Further studies to examine the impact of aspirin on neuropsychological performance and HPA axis function are warranted.