Mortality, morbidity & clinical outcome with different types of vasopressors in out of hospital cardiac arrest patients- a systematic review and meta-analysis.

BACKGROUND & OBJECTIVE: Despite their continued use, the effectiveness and safety of vasopressors in post-cardiac arrest patients remain controversial. This study examined the efficacy of various vasopressors in cardiac arrest patients in terms of clinical, morbidity, and mortality outcomes. METHODS: A comprehensive literature search was performed using online databases (MeSH terms: MEDLINE (Ovid), CENTRAL (Cochrane Library), Embase (Ovid), CINAHL, Scopus, and Google Scholar) from 1997 to 2023 for relevant English language studies. The primary outcomes of interest for this study included short-term survival leading to death, return of spontaneous circulation (ROSC), survival to hospital discharge, neurological outcomes, survival to hospital admission, myocardial infarction, and incidence of arrhythmias. RESULTS: In this meta-analysis, 26 studies, including 16 RCTs and ten non-RCTs, were evaluated. The focus was on the efficacy of epinephrine, vasopressin, methylprednisolone, dopamine, and their combinations in medical emergencies. Epinephrine treatment was associated with better odds of survival to hospital discharge (OR = 1.52, 95%CI [1.20, 1.94]; p < 0.001) and achieving ROSC (OR = 3.60, 95% CI [3.45, 3.76], P < 0.00001)) over placebo but not in other outcomes of interest such as short-term survival/ death at 28-30 days, survival to hospital admission, or neurological function. In addition, our analysis indicates non-superiority of vasopressin or epinephrine vasopressin-plus-epinephrine therapy over epinephrine monotherapy except for survival to hospital admission where the combinatorial therapy was associated with better outcome (0.76, 95%CI [0.64, 0.92]; p = 0.004). Similarly, we noted the non-superiority of vasopressin-plus-methylprednisolone versus placebo. Finally, while higher odds of survival to hospital discharge (OR = 3.35, 95%CI [1.81, 6.2]; p < 0.001) and ROSC (OR = 2.87, 95%CI [1.97, 4.19]; p < 0.001) favoring placebo over VSE therapy were observed, the risk of lethal arrhythmia was not statistically significant. There was insufficient literature to assess the effects of dopamine versus other treatment modalities meta-analytically. CONCLUSION: This meta-analysis indicated that only epinephrine yielded superior outcomes among vasopressors than placebo, albeit limited to survival to hospital discharge and ROSC. Additionally, we demonstrate the non-superiority of vasopressin over epinephrine, although vasopressin could not be compared to placebo due to the paucity of data. The addition of vasopressin to epinephrine treatment only improved survival to hospital admission.

Vasopressin Initiation as a Second-Line VasoPressor in Early Septic Shock (VISPSS).

BACKGROUND: Vasopressin is recommended as a second-line vasoactive agent for the management of septic shock; however, a paucity of data to guide its optimal use remains. The aim was to evaluate the effect of time-to vasopressin initiation and norepinephrine (NE) dose at vasopressin initiation on clinical outcomes in patients presenting with septic shock. METHODS: This was a multi-centered, retrospective, observational study conducted in patients with septic shock. Patients were divided into 2 groups: patients initiated on vasopressin when NE-equivalent dose (NEE) < 0.25 mcg/kg/min or ≥ 0.25 mcg/kg/min. The primary outcome was time-to-vasopressor discontinuation (hours). Secondary outcomes included 28-day in-hospital mortality, intensive care unit (ICU) length of stay (LOS), fluid balance after 72 hours, and the change in NEE at 12 hours. RESULTS: A total of 302 patients were included in this study. After propensity-score matching, 73 patients in each group were identified for analysis. There was no significant difference in the time-to-vasopressor discontinuation (hours) between the groups (88.8 [55-187.5] vs 86.7 [47-172]); p = 0.7815). Fluid balance (mL) at 72 hours was significantly lower when vasopressin was initiated at NEE < 0.25 mcg/kg/min (1769 [71-7287] vs 5762 [1463-8813]; p = 0.0077). A multivariable linear regression showed shorter time to shock resolution with earlier vasopressin initiation, defined as within 4 hours (p < 0.05). CONCLUSION: In this propensity-score matched cohort, vasopressin initiation at NEE < 0.25 mcg/kg/min was not associated with shorter vasopressor duration. There was a lower fluid balance at 72 hours when vasopressin was initiated at lower NE doses.

Tmem117 in AVP neurons regulates the counterregulatory response to hypoglycemia.

The counterregulatory response to hypoglycemia (CRR), which ensures a sufficient glucose supply to the brain, is an essential survival function. It is orchestrated by incompletely characterized glucose-sensing neurons, which trigger a coordinated autonomous and hormonal response that restores normoglycemia. Here, we investigate the role of hypothalamic Tmem117, identified in a genetic screen as a regulator of CRR. We show that Tmem117 is expressed in vasopressin magnocellular neurons of the hypothalamus. Tmem117 inactivation in these neurons increases hypoglycemia-induced vasopressin secretion leading to higher glucagon secretion in male mice, and this effect is estrus cycle phase dependent in female mice. Ex vivo electrophysiological analysis, in situ hybridization, and in vivo calcium imaging reveal that Tmem117 inactivation does not affect the glucose-sensing properties of vasopressin neurons but increases ER stress, ROS production, and intracellular calcium levels accompanied by increased vasopressin production and secretion. Thus, Tmem117 in vasopressin neurons is a physiological regulator of glucagon secretion, which highlights the role of these neurons in the coordinated response to hypoglycemia.

Timing of vasopressin initiation and mortality in patients with septic shock: analysis of the MIMIC-III and MIMIC-IV databases.

BACKGROUND: vasopressin is commonly used as a second-line vasopressor for patients with septic shock, but the optimal timing of initiation is uncertain. This study was designed to investigate when vasopressin initiation may be beneficial for 28-day mortality in septic shock patients. METHODS: This was a retrospective observational cohort study from the MIMIC-III v1.4 and MIMIC-IV v2.0 databases. All adults diagnosed with septic shock according to Sepsis-3 criteria were included. Patients were stratified into two groups based on norepinephrine (NE) dose at the time of vasopressin initiation, defined as the low doses of NE group (NE<0.25 µg/kg/min) and the high doses of NE group (NE ≥ 0.25 µg/kg/min). The primary end-point was 28-day mortality after diagnosis of septic shock. The analysis involved propensity score matching (PSM), multivariable logistic regression, doubly robust estimation, the gradient boosted model, and an inverse probability-weighting model. RESULTS: A total of 1817 eligible patients were included in our original cohort (613 in the low doses of NE group and 1204 in the high doses of NE group). After 1:1 PSM, 535 patients from each group with no difference in disease severity were included in the analysis. The results showed that vasopressin initiation at low doses of NE was associated with reduced 28-day mortality (odds ratio [OR] 0.660, 95% confidence interval [CI] 0.518-0.840, p < 0.001). Compared with patients in the high doses of NE group, patients in the low doses of NE group received significantly shorter duration of NE, with less intravenous fluid volume on the first day after initiation of vasopressin, more urine on the second day, and longer mechanical ventilation-free days and CRRT-free days. Nevertheless, there were no significant differences in hemodynamic response to vasopressin, duration of vasopressin, and ICU or hospital length of stay. CONCLUSIONS: Among adults with septic shock, vasopressin initiation when low-dose NE was used was associated with an improvement in 28-day mortality.

Vasopressin-Induced Hyponatremia in Infants Following Cardiovascular Surgery.

BACKGROUND: Vasopressin is increasingly used in infants following cardiac surgery. Hyponatremia is a noted adverse event, but incidence and risk factors remain undefined. OBJECTIVE: The primary objective was to identify the incidence of vasopressin-induced hyponatremia. Secondary objectives included comparing baseline and change in serum sodium concentrations between infants receiving vasopressin with and without hyponatremia, and comparing vasopressin dose, duration, and clinical characteristics in those with and without hyponatremia. METHODS: This Institutional Review Board-approved, retrospective case-control study included infants <6 months following cardiac surgery receiving vasopressin for ≥6 hours at a tertiary care, academic hospital. Patients who developed hyponatremia, cases, were matched to controls in a 1:2 fashion. Demographics and clinical characteristics were collected. Descriptive and inferential statistics were employed. A conditional logistic regression was used to assess odds of hyponatremia. RESULTS: Of the included 142 infants, 20 (14.1%) developed hyponatremia and were matched with 40 controls. There was significant difference in median nadir between controls and cases, 142.0 versus 128.5 mEq/L (<0.001). A significantly higher number of cases received corticosteroids, loop diuretics, and chlorothiazide versus controls. The regression analysis demonstrated that each additional hour of vasopressin increased the odds of developing hyponatremia by 5% (adjusted odds ratio 1.05 [confidence interval 1-1.1]). CONCLUSIONS AND RELEVANCE: Vasopressin-induced hyponatremia incidence was <15%. Vasopressin duration was independently associated with hyponatremia development.

Incidence of Hypotension Associated With Two Different Vasopressin Discontinuation Strategies in the Recovery Phase of Septic Shock.

Introduction: Safe and effective vasopressor withdrawal strategies during the recovery phase of septic shock lack consensus and are not addressed in clinical practice guidelines. The purpose of this study was to compare the incidence of clinically relevant hypotension associated with different vasopressin (AVP) discontinuation strategies. Methods: This was a single-center, retrospective, cohort study, conducted at a university medical center over a three-year period. Adult patients ≥18 years with septic shock were included in the study. Patients were stratified into two groups; patients incrementally weaned from AVP and patients in which AVP was abruptly discontinued. The primary endpoint was to compare the incidence of clinically relevant hypotension between study groups up to 24 hours following discontinuation. Secondary analyses included the incidence of any hypotensive event up to 24 hours after AVP cessation, intensive care unit and hospital length of stay, and in-hospital mortality. Results: A total of 74 patients (n = 46 AVP wean and n = 28 AVP no-wean) met inclusion criteria and were included in the study. The primary outcome was not statistically different between groups. Clinically relevant hypotension occurred in 24 patients (52.3%) and 16 patients (57.1%) in the AVP wean and AVP no-wean groups, respectively (P = .68). There were no significant differences in any secondary clinical outcome between the two study groups. Conclusion: No differences were found in the incidence of clinically relevant hypotension, length of stay, or mortality between AVP weaning and no-weaning discontinuation strategies. These findings suggest incremental weaning and abrupt withdrawal of AVP are both acceptable discontinuation strategies.

High-dose vasoactive agents in aeromedical retrievals for septic shock: A role for vasopressin?

OBJECTIVE: To determine the number of patients retrieved by aeromedical teams for septic shock requiring vasopressor support who meet criteria for vasopressin therapy under the Surviving Sepsis Campaign 2021 guidelines. METHODS: Retrospective chart review of patients transferred by LifeFlight Retrieval Medicine on vasopressors over 2 years. RESULTS: One thousand one hundred and fifty-eight patients were retrieved on vasopressor therapy, with 428 requiring infusions for septic shock. One hundred and fifteen of these met criteria for administration of vasopressin under Surviving Sepsis Campaign guidelines. CONCLUSION: A sufficient percentage of patients on vasopressors for septic shock require vasopressin therapy to meet current best treatment guidelines, and the inclusion of vasopressin in retrieval drug kits should be considered by Australian aeromedical services.

ACE-Inhibitor or ARB-Induced Refractory Hypotension Treated With Vasopressin in Patients Undergoing General Anesthesia for Dentistry: Two Case Reports.

Two case reports present the use of vasopressin for treating refractory hypotension associated with continued angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) therapy prior to general anesthesia for oral surgery. Both patients were treated in an ambulatory dental surgery clinic and took either their ACEI or ARB medication for hypertension within 24 hours prior to undergoing an intubated general anesthetic. Persistent profound hypotension was encountered intraoperatively that was refractory to treatment with traditional methods. However, the ACEI- or ARB-induced refractory hypotension was successfully managed with the administration of vasopressin.

Optimal target blood pressure in elderly with septic shock (OPTPRESS) trial: study protocol for a randomized controlled trial.

BACKGROUND: Hemodynamic stabilization is a core component in the resuscitation of septic shock. However, the optimal target blood pressure remains debatable. Previous randomized controlled trials suggested that uniformly adopting a target mean arterial pressure (MAP) higher than 65 mmHg for all adult septic shock patients would not be beneficial; however, it has also been proposed that higher target MAP may be beneficial for elderly patients, especially those with arteriosclerosis. METHODS: A multicenter, pragmatic single-blind randomized controlled trial will be conducted to compare target MAP of 80-85 mmHg (high-target) and 65-70 mmHg (control) in the resuscitation of septic shock patients admitted to 28 hospitals in Japan. Patients with septic shock aged ≥65 years are randomly assigned to the high-target or control groups. The target MAP shall be maintained for 72 h after randomization or until vasopressors are no longer needed to improve patients' condition. To minimize the adverse effects related to catecholamines, if norepinephrine dose of ≥ 0.1 µg/kg/min is needed to maintain the target MAP, vasopressin will be initiated. Other therapeutic approaches, including fluid administration, hydrocortisone use, and antibiotic choice, will be determined by the physician in charge based on the latest clinical guidelines. The primary outcome is all-cause mortality at 90 days after randomization. DISCUSSION: The result of this trial will provide great insight on the resuscitation strategy for septic shock in the era of global aged society. Also, it will provide the better understanding on the importance of individualized treatment strategy in hemodynamic management in critically ill patients. TRIAL REGISTRATION: UMIN Clinical Trials Registry; UMIN000041775. Registered 13 September 2020.

Analysis of the Frequency and Onset Time of Hyponatremia/Syndrome of Inappropriate Antidiuretic Hormone Induced by Antidepressants or Antipsychotics.

BACKGROUND: Hyponatremia and syndrome of inappropriate antidiuretic hormone (SIADH) is a potentially fatal adverse effect of antidepressants (ADs) and antipsychotics (APs), although its frequency and onset time have not been well documented. OBJECTIVE: To analyze the frequency and onset time of AD- or AP-induced hyponatremia/SIADH. METHODS: We used plural data-mining techniques to search the US Food and Drug Administration Adverse Event Reporting System (FAERS) database for reports on hyponatremia/SIADH induced by psychotropic drugs from January 2004 to June 2020. For each item, we assessed the reporting odds ratio, 95% CI, median onset time, and Weibull distribution parameters. RESULTS: We identified 36 422 reports related to hyponatremia/SIADH. Signals were detected for all psychotropic drugs that we analyzed, except for clozapine. The median onset time of total AD-induced hyponatremia/SIADH was shorter than that of AP. For all ADs and APs except clozapine, hazards were considered to be the early failure type. In contrast, the hazard of clozapine was considered to be the random failure type. The limitations of this study included several reporting biases and the presence of confounding variables, particularly age. CONCLUSION AND RELEVANCE: Most ADs and APs were found to be associated with a risk for hyponatremia/SIADH. In addition, sufficient attention should be paid to signs of hyponatremia/SIADH in the early phase when most ADs and APs are administered. These data are potentially useful for determining AD- or AP-induced hyponatremia/SIADH in the early stage and for preventing its further aggravation into a serious condition.

Effect of Vasopressin and Methylprednisolone vs Placebo on Return of Spontaneous Circulation in Patients With In-Hospital Cardiac Arrest: A Randomized Clinical Trial.

Importance: Previous trials have suggested that vasopressin and methylprednisolone administered during in-hospital cardiac arrest might improve outcomes. Objective: To determine whether the combination of vasopressin and methylprednisolone administered during in-hospital cardiac arrest improves return of spontaneous circulation. Design, Setting, and Participants: Multicenter, randomized, double-blind, placebo-controlled trial conducted at 10 hospitals in Denmark. A total of 512 adult patients with in-hospital cardiac arrest were included between October 15, 2018, and January 21, 2021. The last 90-day follow-up was on April 21, 2021. Intervention: Patients were randomized to receive a combination of vasopressin and methylprednisolone (n = 245) or placebo (n = 267). The first dose of vasopressin (20 IU) and methylprednisolone (40 mg), or corresponding placebo, was administered after the first dose of epinephrine. Additional doses of vasopressin or corresponding placebo were administered after each additional dose of epinephrine for a maximum of 4 doses. Main Outcomes and Measures: The primary outcome was return of spontaneous circulation. Secondary outcomes included survival and favorable neurologic outcome at 30 days (Cerebral Performance Category score of 1 or 2). Results: Among 512 patients who were randomized, 501 met all inclusion and no exclusion criteria and were included in the analysis (mean [SD] age, 71 [13] years; 322 men [64%]). One hundred of 237 patients (42%) in the vasopressin and methylprednisolone group and 86 of 264 patients (33%) in the placebo group achieved return of spontaneous circulation (risk ratio, 1.30 [95% CI, 1.03-1.63]; risk difference, 9.6% [95% CI, 1.1%-18.0%]; P = .03). At 30 days, 23 patients (9.7%) in the intervention group and 31 patients (12%) in the placebo group were alive (risk ratio, 0.83 [95% CI, 0.50-1.37]; risk difference: -2.0% [95% CI, -7.5% to 3.5%]; P = .48). A favorable neurologic outcome was observed in 18 patients (7.6%) in the intervention group and 20 patients (7.6%) in the placebo group at 30 days (risk ratio, 1.00 [95% CI, 0.55-1.83]; risk difference, 0.0% [95% CI, -4.7% to 4.9%]; P > .99). In patients with return of spontaneous circulation, hyperglycemia occurred in 77 (77%) in the intervention group and 63 (73%) in the placebo group. Hypernatremia occurred in 28 (28%) and 27 (31%), in the intervention and placebo groups, respectively. Conclusions and Relevance: Among patients with in-hospital cardiac arrest, administration of vasopressin and methylprednisolone, compared with placebo, significantly increased the likelihood of return of spontaneous circulation. However, there is uncertainty whether this treatment results in benefit or harm for long-term survival. Trial Registration: ClinicalTrials.gov Identifier: NCT03640949.

Vasoactive Agents for the Management of Acute Variceal Bleeding: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: Vasoactive agents with endoscopic therapy are used to treat acute variceal bleeding (AVB). There are two main groups of vasoactive agents: terlipressin and vasopressin (T-V), and octreotide and somatostatin (O-S). However, the benefit/harm balance is unclear. Our aim was to assess the efficacy and safety of T-V versus O-S for the management of AVB. METHODS: We performed a systematic search for randomized controlled trials (RCTs) in PubMed, Scopus, and CENTRAL. Our main outcomes were mortality and adverse events. Secondary outcomes were bleeding control, rebleeding, blood transfusion, hospital stay. We evaluated the certainty of evidence using GRADE methodology. RESULTS: We included 21 RCTs. The risk of mortality (RR: 1.01; 95%CI: 0.83-1.22), bleeding control (RR: 0.96; 95%CI: 0.91-1.02; I 2 =53%), early rebleeding (RR: 0.91; 95%CI: 0.66-1.24: I 2 =0%), late rebleeding (RR: 0.94; 95 CI: 0.56-1.60; I 2 =0%), blood transfusion (MD: 0.04; 95%CI: -0.31-0.39; I 2 =68%) and hospital stay (MD: -1.06; 95%CI: -2.80-0.69; I 2 =0%) were similar between T-V and O-S groups. Only 15 studies reported adverse events, which were significantly higher in the T-V compared to the O-S group (RR 2.39; 95%CI: 1.58-3.63; I 2 =57%). The certainty of evidence was moderate for the main outcomes, and low or very low for others. CONCLUSIONS: In cirrhotic patients with AVB, those treated with T-V had similar mortality risk compared to O-S. However, the use of T-V showed an increased risk of adverse events compared to O-S.

[SYNDROME OF INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION AS A SIDE EFFECT OF CHEMOTHERAPY FOR URACHAL CARCINOMA: A CASE REPORT].

A 54-year-old woman was admitted to our hospital complaining of gross hematuria and difficulty urinating. Cystoscopy revealed a tumor 4 cm in size with calcification on top of the bladder. After diagnosis of urachal carcinoma by transurethral resection of the bladder, partial cystectomy with en bloc resection of the median umbilical ligament and pelvic lymphadenectomy was performed. Pathological diagnosis confirmed urachal carcinoma, pT3b, ly1, v0, pN1, RM0. TS-1 and cisplatin chemotherapy (TS-1 at 100 mg/day on days 1-21, CDDP at 60 mg/m2 on day 8) was administered. On day 13, the patient was admitted because of consciousness disorder (Glasgow Coma Scale E2V1M4). Hyponatremia (Na 109 mEq/l) and renal excretion of sodium were present and the patient was diagnosed with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) induced by chemotherapy. Serum sodium level and her consciousness level gradually improved after administration of 3% saline. SIADH caused by chemotherapy containing cisplatin is a relatively rare, but potentially serious adverse effect that requires close attention.

Efficacy and safety of corticosteroid therapy in patients with cardiac arrest: a systematic review of randomised controlled trials.

PURPOSES: The role of corticosteroid therapy in patients with cardiac arrest (CA) is uncertain. We aimed to evaluate the efficacy and safety of corticosteroid therapy in CA patients. METHODS: Randomised controlled trials were identified using PubMed, EMBASE, Cochrane Central Register of Controlled Trials, the Chinese National Knowledge Infrastructure and the Chinese Biomedical Literature Database. The primary outcome was overall survival. Secondary outcomes were positive neurological status and probability of sustained restoration of spontaneous circulation (ROSC). Complications were infection and bleeding. Given the significant heterogeneity across previous studies, combining the data using meta-analysis was deemed not appropriate. RESULTS: Five studies (551 patients) met the criteria. Two studies of co-intervention therapy (corticosteroid, vasopressin and epinephrine protocol) found that this approach could benefit in-hospital CA patient survival rates at hospital discharge, improve neurological function at hospital discharge and yield sustained ROSC rate. However, further two studies failed to demonstrate that corticosteroid therapy alone could improve survival and neurological outcomes among CA patients. Additionally, corticosteroid therapy did not increase the risk of infection and bleeding. CONCLUSIONS: Due to the inherent limitations of the studies in this review, we have not been able to reach definitive conclusions. Larger-scale and better-designed studies are therefore recommended, to further evaluate the potential and rational use of corticosteroid therapy in CA patients.

Vasopressor-Sparing Action of Methylene Blue in Severe Sepsis and Shock: A Narrative Review.

Shock is a serious acute circulatory failure leading to inadequate oxygen delivery to the cells. Its treatment is mainly based on circulating fluid optimization, and vasopressors to provide an adequate mean arterial pressure and microcirculatory flow. Norepinephrine is the drug of choice, but high dosages may be responsible for several side effects, including increased myocardial oxygen consumption, dysrhythmias, and peripheral and organ ischemia. Moreover, some patients are "non-responders" to first-line norepinephrine treatment. Hence, other drugs have been proposed to reach and maintain the hemodynamic target. In general, they are described as catecholamine-sparing agents. Among others, the most used are vasopressin, corticosteroids, and angiotensin II. Methylene blue (MB) represents a further option, even though its use is still a topic of controversy. This review article tries to summarize what is known and unknown about the actions of MB in patients in shock. It reduces excessive production of nitric oxide via blockade of guanylate cyclase in shock states. At present, it appears the MB provides positive results in septic shock, if administered early. Further randomized controlled trials are warranted regarding its use to provide more precise indications to physicians involved in the treatment of such patients.

Drinking to death: Hyponatraemia induced by synthetic phenethylamines.

Synthetic phenethylamines are widely abused drugs, comprising new psychoactive substances such as synthetic cathinones, but also well-known amphetamines such as methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy). Cathinones and amphetamines share many toxicodynamic mechanisms. One of their potentially life-threatening consequences, particularly of MDMA, is serotonin-mediated hyponatraemia. Herein, we review the state of the art on phenethylamine-induced hyponatremia; discuss the mechanisms involved; and present the preventive and therapeutic measures. Hyponatraemia mediated by phenethylamines results from increased secretion of antidiuretic hormone (ADH) and consequent kidney water reabsorption, additionally involving diaphoresis and polydipsia. Data for MDMA suggest that acute hyponatraemia elicited by cathinones may also be a consequence of metabolic activation. The literature often reveals hyponatraemia-associated complications such as cerebral oedema, cerebellar tonsillar herniation and coma that may evolve to a fatal outcome, particularly in women. Ready availability of fluids and the recommendation to drink copiously at the rave scene to counteract hyperthermia, often precipitate water intoxication. Users should be advised about the importance of controlling fluid intake while using phenethylamines. At early signs of adverse effects, medical assistance should be promptly sought. Severe hyponatraemia (<130 mmol sodium/L plasma) may be corrected with hypertonic saline or suppression of fluid intake. Also, clinicians should be made aware of the hyponatraemic potential of these drugs and encouraged to report future cases of toxicity to increase knowledge on this potentially lethal outcome.

Aldosterone Decreases Vasopressin-Stimulated Water Reabsorption in Rat Inner Medullary Collecting Ducts.

Aldosterone indirectly regulates water reabsorption in the distal tubule by regulating sodium reabsorption. However, the direct effect of aldosterone on vasopressin-regulated water and urea permeability in the rat inner medullary collecting duct (IMCD) has not been tested. We investigated whether aldosterone regulates osmotic water permeability in isolated perfused rat IMCDs. Adding aldosterone (500 nM) to the bath significantly decreased osmotic water permeability in the presence of vasopressin (50 pM) in both male and female rat IMCDs. Aldosterone significantly decreased aquaporin-2 (AQP2) phosphorylation at S256 but did not change it at S261. Previous studies show that aldosterone can act both genomically and non-genomically. We tested the mechanism by which aldosterone attenuates osmotic water permeability. Blockade of gene transcription with actinomycin D did not reverse aldosterone-attenuated osmotic water permeability. In addition to AQP2, the urea transporter UT-A1 contributes to vasopressin-regulated urine concentrating ability. We tested aldosterone-regulated urea permeability in vasopressin-treated IMCDs. Blockade of gene transcription did not reverse aldosterone-attenuated urea permeability. In conclusion, aldosterone directly regulates water reabsorption through a non-genomic mechanism. Aldosterone-attenuated water reabsorption may be related to decreased trafficking of AQP2 to the plasma membrane. There may be a sex difference apparent in the inhibitory effect of aldosterone on water reabsorption in the inner medullary collecting duct. This study is the first to show a direct effect of aldosterone to inhibit vasopressin-stimulated osmotic water permeability and urea permeability in perfused rat IMCDs.

Oxytocin, Vasopressin and Prolactin in New Breastfeeding Mothers: Relationship to Clinical Characteristics and Infant Weight Loss.

BACKGROUND: Maternal milk production requires the neuropeptide oxytocin. Individual variation in oxytocin function is a compelling target for understanding low milk production, a leading cause of breastfeeding attrition. Complicating the understanding of oxytocin pathways is that vasopressin may interact with oxytocin receptors, yet little is known about the role of vasopressin in lactation. RESEARCH AIMS: The aims of this study were (1) to describe maternal plasma oxytocin, vasopressin, and prolactin patterns during breastfeeding following low-risk spontaneous labor and birth in healthy first-time mothers and (2) to relate hormone patterns to maternal characteristics and breastfeeding measures. METHODS: Eligible women were recruited before hospital discharge. Forty-six participants enrolled and 35 attended the study visit. Participants kept a journal of breastfeeding frequency, symptoms of lactogenesis, and infant weight. Plasma samples were obtained at breastfeeding onset on Day 4-5 postpartum, and repeated after 20 min. Hormones were measured with immunoassays. Infant weight change, milk transfer, and onset of lactogenesis were also measured. RESULTS: Baseline oxytocin and vasopressin were inversely related to one another. Oxytocin and prolactin increased significantly across the 20-min sampling period while vasopressin decreased. Higher oxytocin was associated with higher maternal age, lower BMI, shorter active labor, physiologic labor progression, and less weight loss in the newborn. Higher vasopressin correlated with younger maternal age, higher BMI, and greater newborn weight loss. CONCLUSIONS: Oxytocin and vasopressin have contrasting relationships with maternal clinical characteristics and newborn weight gain in early breastfeeding infants. Further study is needed to understand how oxytocin and vasopressin influence lactation outcomes.

Vasopressin Administration Is Associated With Rising Serum Lactate Levels in Patients With Sepsis.

BACKGROUND: Vasopressin is used in conjunction with norepinephrine during treatment of patients with septic shock. Serum lactate is often used in monitoring of patients with sepsis; however, its importance as a therapeutic target is unclear. The objective of this study is to examine the relationship of vasopressin use on serum lactate levels in patients with sepsis. METHODS: This study uses electronic heath records available via the Medical Information Mart for Intensive Care III. Patients were required to have a serum lactate monitoring during the intensive care unit (ICU) stay. The treatment was the administration of vasopressin between hours 3 and 18 of the ICU stay. Analysis was performed using a matched design. RESULTS: Patients receiving vasopressin were more likely to have their serum lactate levels rise when compared to matched patients who did not receive vasopressin (odds ratio: 6.6; 95% confidence interval: 3.0-14.6, P < .001). Patients who received vasopressin had a median increase in serum lactate of 0.3 mmol/L, while patients who did not receive vasopressin had a median decrease in serum lactate of 0.7 mmol/L (P < .001). There was no statistically significant difference between the control and treated groups' lactate trajectories prior to possible administration of vasopressin (P = .15). The results did not change significantly when norepinephrine initiation was used as the index time. CONCLUSIONS: In patients with sepsis, the administration of vasopressin was associated with a statistically significant difference in lactate change over the course of 24 hours when compared to matched patients who did not receive vasopressin.