Intraoperative hypovolemia as a possible precipitating factor for pituitary apoplexy: a case report.

BACKGROUND: Pituitary apoplexy is acute infarction with or without hemorrhage of the pituitary gland. It is a rare but potentially life-threatening emergency that most commonly occurs in the setting of pituitary adenoma. The mechanisms underlying pituitary apoplexy are not well understood, but are proposed to include factors of both hemodynamic supply and adenoma demand. In the case of patients with known pituitary macroadenomas undergoing major surgery for other indications, there is a theoretically increased risk of apoplexy in the setting of "surgical stress." However, risk stratification of patients with nonfunctioning pituitary adenomas prior to major surgery is challenging because the precipitating factors for pituitary apoplexy are not completely understood. Here we present a case in which intraoperative hypovolemia is a possible mechanistic precipitating factor for pituitary apoplexy. CASE PRESENTATION: A 76-year-old patient with a known hypofunctioning pituitary macroadenoma underwent nephrectomy for renal cell carcinoma, during which there was significant intraoperative blood loss. He became symptomatic with ophthalmoplegia on the second postoperative day, and was diagnosed with pituitary apoplexy. He was managed conservatively with cortisol replacement therapy, and underwent therapeutic anticoagulation 2 months after pituitary apoplexy for deep vein thrombosis. His ophthalmoplegia slowly resolved over months of follow-up. Pituitary apoplexy did not recur with therapeutic anticoagulation. CONCLUSIONS: When considering the risk of surgery in patients with a known pituitary macroadenoma, an operation with possible high-volume intraoperative blood loss may have increased risk of pituitary apoplexy because intraoperative hypovolemia may precipitate ischemia, infarction, and subsequent hemorrhage. This may be particularly relevant in the cases of elective surgery. Additionally, we found that we were able to therapeutically anticoagulate a patient 2 months after pituitary apoplexy for the management of deep vein thrombosis without recurrence of pituitary apoplexy.

The pathophysiology of uncontrolled hemorrhage in horses.

BACKGROUND: Hemorrhagic shock in horses may be classified in several ways. Hemorrhage may be considered internal versus external, controlled or uncontrolled, or described based on the severity of hypovolemic shock the patient is experiencing. Regardless of the cause, as the severity of hemorrhage worsens, homeostatic responses are stimulated to ameliorate the systemic and local effects of an oxygen debt. In mild to moderate cases of hemorrhage (<15% blood volume loss), physiological adaptations in the patient may not be clinically apparent. As hemorrhage worsens, often in the uncontrolled situation such as a vascular breach internally, the pathophysiological consequences are numerous. The patient mobilizes fluid and reserve blood volume, notably splenic stored and peripherally circulating erythrocytes, to preferentially supply oxygen to sensitive organs such as the brain and heart. When the global and local delivery of oxygen is insufficient to meet the metabolic needs of the tissues, a cascade of cellular, tissue, and organ dysfunction occurs. If left untreated, the patient dies of hemorrhagic anemic shock. CLINICAL IMPORTANCE: An understanding of the pathophysiological consequences of hemorrhagic shock in horses and their clinical manifestations may help the practitioner understand the severity of blood volume loss, the need for referral, the need for transfusion, and potential outcome. In cases of severe acute uncontrolled hemorrhage, it is essential to recognize the clinical manifestations quickly to best treat the patient, which may include humane euthanasia. KEY POINTS: Uncontrolled hemorrhage may be defined as the development of a vascular breach and hemorrhage that cannot be controlled by interventional hemostasis methods such as external pressure, tourniquet, or ligation. Causes of uncontrolled hemorrhage in horses may be due to non-surgical trauma, surgical trauma, invasive diagnostic procedures including percutaneous organ biopsy, coagulopathy, hypertension, cardiovascular anomaly, vascular damage, neoplasia such as hemangiosarcoma, toxicity, or idiopathic in nature. When a critical volume of blood is lost, the respondent changes in heart rate, splenic blood mobilization, and microcirculatory control can no longer compensate for decreasing oxygen delivery to the tissues In spite of organ-specific microvascular responses (eg, myogenic responses, local mediator modulation of microvasculature, etc), all organs experience decreases in blood flow during severe hypovolemia Acute, fatal hemorrhagic shock is characterized by progressive metabolic acidosis, coagulopathy, and hypothermia, often termed the "triad of death," followed by circulatory collapse.

Vancomycin prophylaxis for revision hip arthroplasty in penicillin and cephalosporin sensitive patients: Is dose adjustment necessary in accordance with blood loss and fluid replacement?

OBJECTIVE: The aims of this study were (1) to investigate the changes in the serum concentration of prophylactically administrated vancomycin in the perioperative period of revision hip arthroplasty in penicillin/cephalosporin-allergic patients, (2) to assess whether the postoperative re-administration of vancomycin is needed, and (3) to determine the relationships of vancomycin serum concentration with blood loss, body weight, and fluid replacement in such patients. METHODS: This study consisted of 29 patients (20 females, 9 males; mean age=63.3 years; age range=45-79 years) with a history of penicillin/cephalosporin allergy undergoing revision hip arthroplasty secondary to aseptic loosening or periprosthetic fractures. Serum vancomycin levels were measured (1) before administration of vancomycin, (2) at the time of skin incision, (3) every 1,5 hours thereafter until the end of the operation, (4) during the skin closure, and (5) after three and 12 hours from the initial dosage. Data regarding body weight, amounts of intraoperative blood loss, fluid and blood replacements and postoperative wound drainage were recorded. RESULTS: The average blood loss, fluid replacement, and drain volume were 1280.3±575.8 (500-2700) mL, 2922.6±768.8 (1700-4600) mL, and 480.2±163.7 (200-850) mL, respectively. The mean levels of serum vancomycin were 46.3±21.8 (14.1-80.7) mg/L at the time of skin incision, 17.9±4.7 (9.4-30.9) and 9.8±2.2 (4.3-13.8) mg/L after 1.5 and 3 hours from the beginning of the surgery and 5.1±1.1 (2.9-6.8)mg/L after 12th hour postoperatively. The measured vancomycin levels were below the effective serum concentrations (< 5 mg/L) for 18 patients at 12 hours the administration of the first dose. A moderate level negative correlation between the blood loss/body weight ratio and vancomycin levels was found (p=0.004, r=-0.493). Predictive ROC curve analysis resulted in determining a blood loss volume higher than 1150 ml and a blood loss/body weight ratio higher than 18,5 is significant to estimate the vancomycin level below the minimum effective serum level at 12th hour postoperatively (AUC=0.793±0.16, p=0.009, AUC=0.753) 26±0.12, p=0.025, respectively). CONCLUSION: Evidence from this study has indicated vancomycin concentration at 12th hour is below the effective level in most patients. Thus, earlier repetitive infusion of vancomycin seems to be necessary in penicillin/cephalosporin-allergic patients undergoing revision hip arthroplasty, especially in those with high blood loss. LEVEL OF EVIDENCE: Level III, Therapeutic Study.

Ultrasonographic inferior vena cava diameter response to trauma resuscitation after 1 hour predicts 24-hour fluid requirement.

BACKGROUND: Identification of occult hypovolemia in trauma patients is difficult. We hypothesized that in acute trauma patients, the response of ultrasound-measured minimum inferior vena cava diameter (IVCDMIN), IVC Collapsibility Index (IVCCI), minimum internal jugular diameter (IJVDMIN) or IJV Collapsibility Index (IJVCI) after up to 1 hour of fluid resuscitation would predict 24-hour resuscitation intravenous fluid requirements (24FR). METHODS: An NTI-funded, American Association for the Surgery of Trauma Multi-Institutional Trials Committee prospective, cohort trial was conducted at four Level I Trauma Centers. Major trauma patients were screened for an IVCD of 12 mm or less or IVCCI of 50% or less on initial focused assessment sonographic evaluations for trauma. A second IVCD was obtained 40 minutes to 60 minutes later, after standard-of-care fluid resuscitation. Patients whose second measured IVCD was less than 10 mm were deemed nonrepleted (NONREPLETED), those 10 mm or greater were repleted (REPLETED). Prehospital and initial resuscitation fluids and 24FR were recorded. Demographics, Injury Severity Score, arterial blood gasses, length of stay, interventions, and complications were recorded. Means were compared by ANOVA and categorical variables were compared via χ. Receiver operating characteristic curves analysis was used to compare the measures as 24FR predictors. RESULTS: There were 4,798 patients screened, 196 were identified with admission IVCD of 12 mm or IVCCI of 50% or less, 144 were enrolled. There were 86 REPLETED and 58 NONREPLETED. Demographics, initial hemodynamics, or laboratory measures were not significantly different. NONREPLETED had smaller IVCD (6.0 ± 3.7 mm vs. 14.2 ± 4.3 mm, p < 0.001) and higher IVCCI (41.7% ± 30.0% vs. 13.2% ± 12.7%, p < 0.001) but no significant difference in IJVD or IJVCCI. REPLETED had greater 24FR than NONREPLETED (2503 ± 1751 mL vs. 1,243 ± 1,130 mL, p = 0.003). Receiver operating characteristic analysis indicates IVCDMIN predicted 24FR (area under the curve [AUC], 0.74; 95% confidence interval [CI], 0.64-0.84; p < 0.001) as did IVCCI (AUC, 0.75; 95% CI, 0.65-0.85; p < 0.001) but not IJVDMIN (AUC, 0.48; 95% CI, 0.24-0.60; p = 0.747) or IJVCI (AUC, 0.54; 95% CI, 0.42-0.67; p = 0.591). CONCLUSION: Ultrasound assessed IVCDMIN and IVCCI response initial resuscitation predicts 24-hour fluid resuscitation requirements. LEVEL OF EVIDENCE: Diagnostic tests or criteria, level II.

Rapid saline infusion and/or drinking enhance skin sympathetic nerve activity components reduced by hypovolaemia and hyperosmolality in hyperthermia.

KEY POINTS: In hyperthermia, plasma hyperosmolality suppresses both cutaneous vasodilatation and sweating responses and this suppression is removed by oropharyngeal stimulation such as drinking. Hypovolaemia suppresses only cutaneous vasodilatation, which is enhanced by rapid infusion in hyperthermia. Our recent studies suggested that skin sympathetic nerve activity (SSNA) involves components synchronized and non-synchronized with the cardiac cycle, which are associated with an active vasodilator and a sudomotor, respectively. In the present study, plasma hyperosmolality suppressed both components; drinking removed the hyperosmolality-induced suppressions, simultaneously with increases in cutaneous vasodilatation and sweating, while not altering plasma volume and osmolality. Furthermore, a rapid saline infusion increased the synchronized component and cutaneous vasodilatation in hypovolaemic and hyperthermic humans. The results support our idea that SSNA involves an active cutaneous vasodilator and a sudomotor, and that a site where osmolality signals are projected to control thermoregulation is located more superior than the medulla where signals from baroreceptors are projected. ABSTRACT: We reported that skin sympathetic nerve activity (SSNA) involved components synchronized and non-synchronized with the cardiac cycle; both components increased in hyperthermia and our results suggested that the components are associated with an active vasodilator and a sudomotor, respectively. In the present study, we examined whether the increases in the components in hyperthermia would be suppressed by plasma hyperosmolality simultaneously with suppression of cutaneous vasodilatation and sweating and whether this suppression was released by oropharyngeal stimulation (drinking). Also, effects of a rapid saline infusion on both components and responses of cutaneous vasodilatation and sweating were tested in hypovolaemic and hyperthermic subjects. We found that (1) plasma hyperosmolality suppressed both components in hyperthermia, (2) the suppression was released by drinking 200 mL of water simultaneously with enhanced cutaneous vasodilatation and sweating responses, and (3) a rapid infusion at 1.0 and 0.2 ml min-1  kg-1 for the first 10 min and the following 20 min, respectively, increased the synchronized component and cutaneous vasodilatation in diuretic-induced hypovolaemia greater than those in a time control; at 0.1 ml min-1  kg-1 for 30 min no greater increases in the non-synchronized component and sweating responses were observed during rapid infusion than in the time control. The results support the idea that SSNA involves components synchronized and non-synchronized with the cardiac cycle, associated with the active cutaneous vasodilator and sudomotor, and a site of osmolality-induced modulation for thermoregulation is located superior to the medulla where signals from baroreceptors are projected.

Noninvasive monitoring of physiologic compromise in acute appendicitis: New insight into an old disease.

INTRODUCTION: Physiologic compromise in children with acute appendicitis has heretofore been difficult to measure. We hypothesized that the Compensatory Reserve Index (CRI), a novel adjunctive cardiovascular status indicator, would be low for children presenting with acute appendicitis in proportion to their physiological compromise, and that CRI would rise with fluid resuscitation and surgical management of their disease. METHODS: Ninety-four children diagnosed with acute appendicitis were monitored with a CipherOx CRI™ M1 pulse oximeter (Flashback Technologies Inc., Boulder, CO). For clarity, CRI=1 indicates supine normovolemia, CRI=0 indicates hemodynamic decompensation (systolic blood pressure<80mmHg), and CRI values between 1 and 0 indicate the proportion of volume reserve remaining before collapse. Results are presented as counts with proportion (%), or mean with 95% confidence interval (CI). RESULTS: Mean age was 11years old (95% CI: 10-12), and 49 (52%) of the children were male. Fifty-four (57%) had nonperforated appendicitis and 40 (43%) had perforated appendicitis. Mean initial CRI was significantly higher in those with nonperforated appendicitis compared to those with perforated appendicitis (0.57, 95% CI: 0.52-0.63 vs. 0.36, 95% CI: 0.29-0.43; P<0.001). The significant differences in mean CRI values between the two groups remained throughout the course of treatment, but lost its significance at 2h after surgery (0.63, 95% CI: 0.57-0.70 vs. 0.53, 95% CI: 0.46-0.61; P=0.05). CONCLUSION: Low CRI values in children with perforated appendicitis are indicative of their lower reserve capacity owing to peritonitis and hypovolemia. CRI offers a real-time, noninvasive adjunctive tool to monitor tolerance to volume loss in children. LEVEL OF EVIDENCE: Study of diagnostic test; Level of evidence: Level III.

Short-term effects of stored homologous red blood cell transfusion on cardiorespiratory function and inflammation: an experimental study in a hypovolemia model

The pathophysiological mechanisms associated with the effects of red blood cell (RBC) transfusion on cardiopulmonary function and inflammation are unclear. We developed an experimental model of homologous 14-days stored RBC transfusion in hypovolemic swine to evaluate the short-term effects of transfusion on cardiopulmonary system and inflammation. Sixteen healthy male anesthetized swine (68±3.3 kg) were submitted to controlled hemorrhage (25% of blood volume). Two units of non-filtered RBC from each animal were stored under blood bank conditions for 14 days. After 30 min of hypovolemia, the control group (n=8) received an infusion of lactated Ringer's solution (three times the removed volume). The transfusion group (n=8) received two units of homologous 14-days stored RBC and lactated Ringer's solution in a volume that was three times the difference between blood removed and blood transfusion infused. Both groups were followed up for 6 h after resuscitation with collection of hemodynamic and respiratory data. Cytokines and RNA expression were measured in plasma and lung tissue. Stored RBC transfusion significantly increased mixed oxygen venous saturation and arterial oxygen content. Transfusion was not associated with alterations on pulmonary function. Pulmonary concentrations of cytokines were not different between groups. Gene expression for lung cytokines demonstrated a 2-fold increase in mRNA level for inducible nitric oxide synthase and a 0.5-fold decrease in mRNA content for IL-21 in the transfused group. Thus, stored homologous RBC transfusion in a hypovolemia model improved cardiovascular parameters but did not induce significant effects on microcirculation, pulmonary inflammation and respiratory function up to 6 h after transfusion.

A Systematic Review of Neuroprotective Strategies during Hypovolemia and Hemorrhagic Shock.

Severe trauma constitutes a major cause of death and disability, especially in younger patients. The cerebral autoregulatory capacity only protects the brain to a certain extent in states of hypovolemia; thereafter, neurological deficits and apoptosis occurs. We therefore set out to investigate neuroprotective strategies during haemorrhagic shock. This review was performed in accordance to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Before the start of the search, a review protocol was entered into the PROSPERO database. A systematic literature search of Pubmed, Web of Science and CENTRAL was performed in August 2017. Results were screened and evaluated by two researchers based on a previously prepared inclusion protocol. Risk of bias was determined by use of SYRCLE's risk of bias tool. The retrieved results were qualitatively analysed. Of 9093 results, 119 were assessed in full-text form, 16 of them ultimately adhered to the inclusion criteria and were qualitatively analyzed. We identified three subsets of results: (1) hypothermia; (2) fluid therapy and/or vasopressors; and (3) other neuroprotective strategies (piracetam, NHE1-inhibition, aprotinin, human mesenchymal stem cells, remote ischemic preconditioning and sevoflurane). Overall, risk of bias according to SYRCLE's tool was medium; generally, animal experimental models require more rigorous adherence to the reporting of bias-free study design (randomization, etc.). While the individual study results are promising, the retrieved neuroprotective strategies have to be evaluated within the current scientific context-by doing so, it becomes clear that specific promising neuroprotective strategies during states of haemorrhagic shock remain sparse. This important topic therefore requires more in-depth research.

Artificial Hydration at the End of Life.

Initiation or continuation of artificial hydration (AH) at the end of life requires unique considerations. A combination of ethical precedents and medical literature may provide clinical guidance on how to use AH at the end of life. The purpose of this review is to describe the ethical framework for and review current literature relating to the indications, benefits, and risks of AH at the end of life. Provider, patient, and family perspectives will also be discussed.

Validation of a noninvasive monitor to continuously trend individual responses to hypovolemia.

BACKGROUND: Humans are able to compensate for significant blood loss with little change in traditional vital signs, limiting early detection and intervention. We hypothesized that the Compensatory Reserve Index (CRI), a new hemodynamic parameter that trends changes in intravascular volume relative to the individual patient's response to hypovolemia, would accurately trend each subject's progression from normovolemia to decompensation (systolic blood pressure < 80) and back to normovolemia in humans. METHODS: Men and women, ages 19 years to 36 years, underwent stepwise (~333 mL aliquot) removal and replacement of 20% blood volume (men, 15 mL/kg; women, 13 mL/kg) via a large bore intravenous (i.v.) line. During each experiment, subjects were monitored with four CipherOx CRI Tablets. Withdrawn blood was reinfused at the end of each experiment. RESULTS: Forty-two subjects (24 men; 18 women) were enrolled in the study, of which 32 completed the protocol. Seven subjects became symptomatic and collapsed (systolic blood pressure < 80), six never achieving maximum blood loss; each was rescued with a saline infusion followed by reinfusion of their stored blood. The mean CRI at baseline for all 42 subjects was 0.9 ± 0.04. The mean CRI for the 32 subjects while asymptomatic at maximum blood loss was 0.611 ± 0.028. For the asymptomatic subjects, the average blood loss volume was 1018 mL ± 286 mL. In comparison, the mean CRI at maximum blood loss for the seven subjects who collapsed was 0.15 ± 0.007 and their average blood loss volume was 860 ± 183 mL. Mean CRI after reinfusion of blood was 0.89 ± 0.02. In addition symptomatic subjects demonstrated three times larger average decrease in CRI per liter of blood removed, 0.85 versus 0.28 for asymptomatic subjects. CONCLUSION: CRI trends change in intravascular volume relative to an individual's response to hypovolemia and is sensitive to the differing risks associated with individuals' differing tolerance to volume loss. LEVEL OF EVIDENCE: Prognostic study, level II.

Experience in the use of non-pneumatic anti-shock garment (NASG) in the management of postpartum haemorrhage with hypovolemic shock in the Fundación Valle Del Lili, Cali, Colombia.

BACKGROUND: The aim of this case series is to describe the experience of using the non-pneumatic anti-shock garment (NASG) in the management of severe Postpartum hemorrhage (PPH) and shock, and the value of implementing this concept in high-complexity obstetric hospitals. METHODS: Descriptive case series of 77 women that received NASG in the management of PPH with severe hypovolemic shock from June 2014 to December 2015. Vital signs, shock index (SI), the lactic acid value and the base deficit were compared before and after NASG application. RESULTS: Fifty-six (77%) women had an SI > 1.1 at the time shock management was initiated; 96% had uterine atony. All women received standard does of uterotonics. The average time between the birth and NASG applications was 20 min. Forty-eight percent of women recovered haemodynamic variables in the first hour and 100% within the first 6 h; 100% had a SI < 1.0 in the first hour. The NASG was not removed until definitive control of bleeding was achieved, with an average time of use of 24 h. There were no mortalities. CONCLUSIONS: In this case series of women in severe shock, the NASG was an effective management device for the control of severe hypovolemic shock. It should be considered a first-line option for shock management.

Fluid Management in Lung Transplant Patients.

Overall, there is a lack of randomized controlled trials examining the correlation between fluid volume delivery and outcomes in postoperative lung transplant patients. However, using thoracic surgery patients as a guide, the evidence suggests that hypervolemia correlates with pulmonary edema and should be avoided in lung transplant patients. However, it is recognized that patients with hemodynamic instability may require volume for attenuation of this situation, but it can likely be mitigated with the use of inotropic medication to maintain adequate perfusion and avoid the development of edema.

Postoperative volume balance: does stroke volume increase in Trendelenburg's position?

In healthy humans, stroke volume (SV) and cardiac output (CO) do not increase with expansion of the central blood volume by head-down tilt or administration of fluid. Here, we exposed 85 patients to Trendelenburg's position about one hour after surgery while cardiovascular variables were determined non-invasively by Modelflow. In Trendelenburg's position, SV (83 ± 19 versus 89 ± 20 ml) and CO (6·2 ± 1·8 versus 6·8 ± 1·8 l/min; both P<0·05) increased, while heart rate (75 ± 15 versus 76 ± 14 b min-1 ) and mean arterial pressure were unaffected (84 ± 15 versus 84 ± 16 mmHg). For the 33 patients (39%) with a > 10% increase in SV (from 78 ± 16 to 90 ± 17 ml) corresponding to an increase in CO from 5·9 ± 1·5 to 6·9 ± 1·6 l min-1 (P<0·05) when tilted head-down, administration of 250 ml Ringer's lactate solution increased SV (to 88 ± 18 ml) and CO (to 6·8 ± 1·7 l min-1 ). In conclusion, determination of SV and/or CO in Trendelenburg's position can be used to evaluate whether a patient is in need of IV fluid as here exemplified after surgery.

Anemia tolerance during normo-, hypo-, and hypervolemia.

BACKGROUND: Restrictive intraoperative fluid management has been demonstrated to improve outcome of visceral and lung surgery in several studies. However, subsequent hypovolemia (HOV) may be accompanied by a decrease of anemia tolerance, resulting in increased transfusion needs. We therefore investigated the effect of volume status on anemia tolerance. STUDY DESIGN AND METHODS: Eighteen domestic pigs of either sex (mean weight, 23.5 ± 4.8 kg) were anesthetized, ventilated, and randomized into three experimental groups: normovolemia (no intervention), HOV (blood loss of 40% of blood volume), and hypervolemia (HEV; volume infusion of 40% of blood volume). The animals were then hemodiluted until their individual critical hemoglobin concentrations (Hbcrit ) were reached by the exchange of whole blood for hydroxyethyl starch (HES; 130:0.4). Subsequently, organ-specific hypoxia was assessed using pimonidazole tissue staining in relevant organs. Hemodynamic and metabolic variables were also investigated. RESULTS: Despite significant differences in exchangeable blood volume, Hbcrit was the same in all groups (2.3 g/dL, NS). During HOV, tissue hypoxia was aggravated in the myocardium, brain, and kidneys, whereas tissue oxygenation of the liver and intestine was not influenced by volume status. HEV increased tissue hypoxia in the lungs, but did not impact tissue oxygenation of other organs. CONCLUSIONS: The combination of hemorrhagic HOV with subsequent anemia leads to accentuated tissue hypoxia, revealed by a significant increase in pimonidazole binding at Hbcrit , in heart, lungs, brain, and kidney. The lungs were the only organ that showed increased tissue hypoxia after pretreatment of HES infusion and subsequent anemia by normovolemic hemodilution.

Quality and Safety in Health Care, Part XX: Goal-Directed Fluid Therapy and the Universal Protocol.

There have been numerous initiatives to improve quality and safety in surgery. Goal-directed fluid therapy and a quality bundle for emergency laparotomy surgery are two of them. The establishment of a Universal Protocol to prevent the wrong procedure, the wrong patient having a procedure, or the wrong site for a procedure is an important safeguard for patients.

The importance of albumin infusion rate for plasma volume expansion following major abdominal surgery - AIR: study protocol for a randomised controlled trial.

BACKGROUND: Administration of fluids to restore normovolaemia is one of the most common therapeutic interventions performed peri-operatively and in the critically ill, but no study has evaluated the importance of infusion rate for the plasma volume-expanding effect of a resuscitation fluid. The present study is designed to test the hypothesis that a slow infusion of resuscitation fluid results in better plasma volume expansion than a rapid infusion. METHODS/DESIGN: The study is a single-centre, assessor-blinded, parallel-group, randomised prospective study. Patients over 40 years of age admitted to the post-operative care unit after a Whipple procedure or major gynaecological surgery and presenting with signs of hypovolaemia are eligible for inclusion. Patients are randomised in a 1:1 fashion with no stratification to either rapid (30 minutes) or slow (180 minutes) infusion of 5% albumin at a dose of 10 ml/kg ideal body weight. Plasma volume is measured using 125I human serum albumin at baseline (prior to albumin infusion) as well as at 30 minutes and 180 minutes after infusion start. The primary endpoint is change in plasma volume from baseline to 180 minutes after the start of 5% albumin infusion. Secondary endpoints include the integral of plasma volume over time from baseline to 180 minutes after the start of the infusion and transcapillary escape rate of albumin (%/h) from 180 minutes to 240 minutes after the start of albumin infusion. In addition, diuresis, change in central venous oxygen saturation, lactate and blood pressure will be evaluated. A total of 70 patients will be included in the study, and the study has 80% power to detect a difference of 4 ml/kg in plasma volume expansion between the two groups. DISCUSSION: The present study is the first clinical investigation of the importance of infusion rate for the plasma volume-expanding effect of a resuscitation fluid. TRIAL REGISTRATION: EudraCT identifier: 2013-004446-42 . Registration date: 20 December 2013. ClinicalTrials.gov identifier: NCT02728921 . Registration date: 31 March 2016.

Ten pitfalls in the proper management of patients with hyponatremia.

Hyponatremia (serum sodium <135 mEq/L) is a common electrolyte disorder in community or hospitalized patients. Serum sodium levels should be corrected at a proper rate in patients with hyponatremia, since overcorrection of serum sodium levels is related to devastating neurologic consequences, such as the osmotic demyelination syndrome (ODS). However, a number of pitfalls, which could lead to undercorrection or overcorrection of hyponatremia, are common during the treatment of hyponatremic patients. Hereby, we describe ten common pitfalls that are observed during the correction of serum sodium concentration in hyponatremic patients. These refer to pitfalls in the goals and limits of the correction rate of serum sodium, pitfalls in the means (e.g. solutions but also drugs) and formulas used for achieving the desired correction rate and pitfalls associated with inadequate management or overcorrection. The knowledge of these common-in-clinical-practice pitfalls could assist clinicians in the proper management of patients with hyponatremia.