The predictive value of phase angle on long-term outcome after ICU admission.

INTRODUCTION: The use of severity of illness scoring systems, including the Acute Physiology and Chronic Health Evaluation (APACHE) III score, has made it possible to compare groups of patients and evaluate treatment strategies. Phase angle, derived from bio-impedance analysis, reflects tissue quality and quantity in which cell mass, membrane integrity and hydration state are represented. We hypothesized that phase angle on ICU admission may serve as a proxy for physical frailty and as such can be used as an additional predictor of long-term mortality after ICU admission. METHODS: A single-center prospective observational cohort study with consecutive patients, admitted to the ICU between June 2018 and June 2019. Demographic data, APACHE III, comorbidity, and phase angle in the first 6 h after ICU admission were collected and the ICU, hospital, and 1-year survival were registered. RESULTS: Of all 1023 patients, 115 (11%) died within a year after ICU admission. Nonsurvivors had higher APACHE III scores than survivors [86 (65-119) vs. 55 (46-67), p < 0.001]. Phase angle was significantly higher in survivors than in nonsurvivors [5.4 (4.7-6.4) vs. 4.7 (3.9-6.0), p < 0.001]. Univariate analysis showed an association between mortality and admission type, sepsis, presence of malignancy, APACHE III, and PhA. Multivariate logistic regression analysis using these variables confirmed low PhA to be an independent predictor of 1-year mortality (OR: 1.81; CI: 1.09-2.97; p = 0.02), in addition to presence of malignancy (OR: 2.30; CI: 1.31-4.02; p = 0.004) and APACHE III score (OR: 1.03; CI: 1.02-1.04; p < 0.001). CONCLUSION: In this single center study, low phase angle was independently associated with 1-year all-cause mortality after ICU admission. CLINICALTRIALS: gov number: NCT0444976.

Pregnancy-related myocardial infarction.

INTRODUCTION: The risk of acute myocardial infarction in young women is low, but increases during pregnancy due to the physiological changes in pregnancy, including hypercoagulability. Ischaemic heart disease during pregnancy is not only associated with increased maternal morbidity and mortality, but also with high neonatal complications. Advancing maternal age and other risk factors for cardiovascular diseases may further increase the risk of ischaemic heart disease in young women. METHODS: We searched the coronary angiography database of a Dutch teaching hospital to identify women with acute myocardial infarction who presented during pregnancy or postpartum between 2011 and 2013. RESULTS: We found two cases. Both women were in their early thirties and both suffered from myocardial infarction in the postpartum period. Acute myocardial infarction was due to coronary stenotic occlusion in one patient and due to coronary artery dissection in the other patient. Coronary artery dissection is a relatively frequent cause of myocardial infarction during pregnancy. Both women were treated by percutaneous coronary intervention and survived. CONCLUSION: Physicians should be aware of the increased risk of myocardial infarction when encountering pregnant or postpartum women presenting with chest pain.

Prevotella intermedia infection causing acute and complicated aortitis-A case report.

INTRODUCTION: Aortitis is a general term that refers to all conditions involving an inflammation of the aortic wall. This case report describes the surgical approach of a patient with infectious and symptomatic aortitis caused by the rare vector Prevotella intermedia. PRESENTATION OF CASE: A 44-year old male patient was admitted with fever and general discomfort after a period of sore throat in a non-teaching hospital. After two weeks he developed acute abdominal and back pain accompanied by sweating and elevated infection parameters. Computed tomography angiography revealed atherosclerotic changes of the infrarenal aorta with a locally contained rupture of the aorta alongside peri-aortal signs of inflammation (and aortitis aspects). An urgent aortic reconstruction was performed according to Nevelsteen. The blood cultures turned out positive for Prevotella intermedia. Postoperatively the patient received antibiotics for six weeks. The patient recovered uneventful from this infection and surgical procedure. DISCUSSION: A complicated and acute aortitis is a rare but potentially life-threatening disease. The aetiology can be ordered into two main groups; inflammatory and infectious. Diagnosis is based upon symptoms, biochemical values, microbiological results and imaging modalities. Treatment depends on aetiology and should be discussed in an experienced multidisciplinary setting. Infectious aortitis should be treated with antibiotics for at least six weeks with close monitoring of the patient's clinic and biochemical values, even after surgery. CONCLUSION: Prevotella intermedia is a rare causative agent for aortitis. Acute aortitis is a challenging clinical entity which should be managed in an equipped medical center by an experienced multidisciplinary team.

The Development of Intensive Care Unit Acquired Hypernatremia Is Not Explained by Sodium Overload or Water Deficit: A Retrospective Cohort Study on Water Balance and Sodium Handling.

Background. ICU acquired hypernatremia (IAH, serum sodium concentration (sNa) ≥ 143 mmol/L) is mainly considered iatrogenic, induced by sodium overload and water deficit. Main goal of the current paper was to answer the following questions: Can the development of IAH indeed be explained by sodium intake and water balance? Or can it be explained by renal cation excretion? Methods. Two retrospective studies were conducted: a balance study in 97 ICU patients with and without IAH and a survey on renal cation excretion in 115 patients with IAH. Results. Sodium intake within the first 48 hours of ICU admission was 12.5 [9.3-17.5] g in patients without IAH (n = 50) and 15.8 [9-21.9] g in patients with IAH (n = 47), p = 0.13. Fluid balance was 2.3 [1-3.7] L and 2.5 [0.8-4.2] L, respectively, p = 0.77. Urine cation excretion (urine Na + K) was < sNa in 99 out of 115 patients with IAH. Severity of illness was the only independent variable predicting development of IAH and low cation excretion, respectively. Conclusion. IAH is not explained by sodium intake or fluid balance. Patients with IAH are characterized by low urine cation excretion, despite positive fluid balances. The current paradigm does not seem to explain IAH to the full extent and warrants further studies on sodium handling in ICU patients.

Evaluation of a vancomycin dosing protocol for intensive care unit patients.

Vancomycin is a glycopeptide antibiotic that needs to be dosed to achieve target trough levels of 15-20 mg/l. Dosing can be challenging in ICU patients. To optimise therapy, in ICU-pharmacy collaboration, a dosing protocol was introduced on the ICU of the Medical Center Leeuwarden, the Netherlands. The effectiveness in obtaining timely adequate trough levels was evaluated. We retrospectively analysed data from 59 patients. Results show that pharmacy involvement and introduction of the dosing protocol resulted in early adequate trough levels (p = 0.016). Introduction of the protocol alone resulted in non-significant early accurate trough levels. The protocol should be used with caution in patients with a possibly unreliable estimated glomerular filtration rate. Careful protocol introduction is important.

Microcirculatory perfusion derangements during continuous hemofiltration with fixed dose of ultrafiltration in stabilized intensive care unit patients.

INTRODUCTION: Acute kidney injury (AKI) is a well-known complication in critically ill patients. Little is known about the timing and the ultrafiltration dose after initial resuscitation. In vivo microscopy of the microcirculation has been suggested as alternative for the assessment of volume status. Previous studies contribute to the understanding that intravascular hypovolemia is reflected by microcirculatory blood flow changes not detected by conventional methods. The aim of our study was to assess microcirculatory blood flow changes during negative fluid balance ultrafiltration in patients with oliguric AKI. MATERIALS AND METHODS: Patients with oliguric AKI on renal replacement therapy were included after hemodynamic stabilization. Target was a predefined negative fluid balance; subsequently, a stepwise decrease in amount of substitution fluid was achieved. The data were recorded at baseline and after each change. RESULTS: Fifteen patients were included in the study. Microcirculatory blood flow index did not change significantly between baseline and endpoint (2.90 [2.87-3.00] vs 2.90 [2.75-3.00], P=.57). During treatment, heart rate decreased from 96 (80-111) to 94 (79-110) beats per minute (P=.01), without a significant change in mean arterial blood pressure (80 [68-95 mm Hg] vs 79 [65-91 mm Hg], P=.5). CONCLUSION: Microcirculatory blood flow is not altered by reduced substitution during renal replacement therapy.

Rectal microcirculatory alterations after elective on-pump cardiac surgery.

BACKGROUND: Hemodynamic changes, related to on-pump cardiac surgery, have been reported to impair intestinal perfusion. However, until recently, direct in vivo observation of the intestinal microcirculation was not clinically feasible, and the concept of altered intestinal blood flow in the setting of cardiac surgery depended on indirect observations from other techniques, such as tonometry and microdialysis. To establish the incidence of intestinal microvascular alterations after cardiac surgery, we performed direct in vivo observation of the microcirculation in a clinically accessible part of the intestinal tract in this setting. METHODS: A single-center prospective observational study was conducted in postoperative elective on-pump cardiac surgery patients. Simultaneously, sidestream dark field (SDF) imaging and automated gas tonometry were performed in the rectal pouch within 30 minutes after ICU admission. RESULTS: The rectal median microvascular flow index was 3(3-3) and the proportion of perfused vessels (PPV) was 85% (72-93). The median rectal-to-arterial partial carbon dioxide pressure difference (ΔPCO(2)) was 1.5 (-1.5-8.3) mmHg; 6 (21%) patients had a ΔPCO(2)> 8.3 mmHg, among them 2 (7%) with values> 10.5 mmHg. CONCLUSION: After elective on-pump cardiac surgery, direct in vivo observation of rectal mucosa revealed a PPV <90% in 54% of all patients. At the same time, rectal microcirculatory blood flow appeared to be unaltered. Combining rectal SDF imaging with rectal tonometry revealed a 7% incidence of rectal-to-arterial pCO(2) gap >1.4,kPa, suggesting non-dysoxic perfusion in the majority of patients, despite the observed percentage of non-perfused crypts.

11beta-hydroxysteroid dehydrogenase activity in proteinuric patients and the effect of angiotensin-II receptor blockade.

BACKGROUND: It has been suggested that an altered setpoint of the 11betaHSD-mediated cortisol to cortisone interconversion towards cortisol contributes to sodium retention in nephrotic syndrome patients. We studied the parameters of 11betaHSD activity in proteinuric patients, in particular its activity at the kidney level. We also studied the effect of angiotensin-II receptor blockade on the parameters of 11betaHSD activity. MATERIALS AND METHODS: Serum cortisol/cortisone ratio and the urinary ratios of (tetrahydrocortisol + allo-tetrahydrocortisol)/tetrahydrocortisone [(THF + allo-THF)/THE] and of urinary free cortisol/free cortisone (UFF/UFE) were measured in eight proteinuric patients and compared with eight matched, healthy subjects. Patients were subsequently studied after 4 weeks' treatment with losartan 50 mg day-1 and placebo, respectively. RESULTS: No significant differences between the proteinuric patients and the healthy subjects were observed in the serum cortisol, serum cortisone, serum cortisol to cortisone ratio, or in the urinary excretions of THF, allo-THF, THE, sum of cortisol metabolites, or the (THF + allo-THF)/THE ratio. Urinary free cortisol excretion and the UFF/UFE ratio were lower in the proteinuric patients than in the healthy subjects (56 +/- 21 vs. 85 +/- 24 pmol min-1, P < 0.05, and 0.39 +/- 0.07 vs. 0.63 +/- 0.28, P < 0.05, respectively). Mean arterial pressure and proteinuria were reduced significantly during losartan treatment, but without concomitant changes in peripheral cortisol metabolism. CONCLUSIONS: Increased renal inactivation of cortisol in proteinuric patients does not support the contention that altered 11betaHSD activity contributes to sodium retention in patients with nephrotic syndrome. Losartan 50 mg d.d. reduces mean arterial pressure and proteinuria, but does not exert a significant effect on the cortisol to cortisone interconversion.

Time course of the antiproteinuric and renal haemodynamic responses to losartan in microalbuminuric IDDM.

BACKGROUND: Interference in the renin-angiotensin system with angiotensin-converting enzyme (ACE) inhibitors has proven to be effective in lowering albuminuria in patients with insulin-dependent diabetes mellitus (IDDM). We studied whether angiotensin II receptor antagonism reduces urinary albumin excretion (UAE) in IDDM patients, and the relationship between the antiproteinuric effect and changes in systemic and renal haemodynamics. METHODS: Nine IDDM patients with microalbuminuria (30-300 mg/24 h) were studied. Patients were studied after a 4 week placebo period, on days 3, 7 and 28 of treatment with losartan 50 mg once daily, and after a 4 week placebo-controlled recovery period. RESULTS: Mean arterial pressure (MAP) was only slightly lowered during losartan treatment. Effective renal plasma flow (ERPF) was significantly increased on the third day of treatment and remained stable throughout the treatment period. Glomerular filtration rate (GFR) did not change throughout the study. Filtration fraction (FF) was maximally lowered on the third day of treatment and remained stable during treatment. UAE was already significantly lowered after 2 days of treatment, during both the day and night, and remained stable throughout the treatment period. The time course of the changes in UAE paralleled that of the changes in MAP, ERPF and FF. CONCLUSIONS: The angiotensin receptor antagonist losartan effectively lowers UAE in microalbuminuric IDDM patients. The changes observed in renal haemodynamics and UAE are concordant in time and maximal within only a few days of treatment. These results support the importance of the specific effects of interference in the renin angiotensin system (RAS) in microalbuminuric IDDM on blood pressure and renal haemodynamics in reducing urinary protein leakage, rather than non-haemodynamic, structural changes of the glomerular basement membrane.

Pharmacokinetics and pharmacodynamics of candesartan cilexetil in patients with normal to severely impaired renal function.

OBJECTIVE: We studied the pharmacokinetics and pharmacodynamics of single and multiple doses of candesartan cilexetil 8 mg per day in hypertensive patients with different degrees of renal function impairment. Candesartan is an angiotensin II subtype 1 (AT1) receptor antagonist that is administered orally as candesartan cilexetil which is converted in the active compound. METHODS: Twenty-three patients were included, divided into groups according to creatinine clearance (cr cl. group A >60 nl x min(-1) x 1.73 m(-2), group B 30-60 ml x min(-1) x 1.73 m(-2) and group C 15-30 ml x min(-1) x 1.73 m(-2)). RESULTS: Trough serum concentrations of candesartan were higher in group C compared with group A. The values did not increase after multiple dosing, indicating absence of accumulation. There was a significant negative correlation between the area under the concentration-time curve extrapolated to time infinity (AUCinf) and the glomerular filtration rate (GFR) indicating a lower renal clearance of candesartan in patients with impaired renal function. The onset of haemodynamic and hormonal effects was gradual. During the single-dose study blood pressure as well as plasma renin activity (PRA) and angiotensin II were unchanged at peak. At day 5 of the multiple-dose study blood pressure was lower and both PRA and angiotensin II were higher compared with baseline. CONCLUSION: Although serum trough levels increased during repeated administration and half-life was higher in patients with impaired renal function, candesartan cilexetil at a dose of 8 mg per day does not lead to drug accumulation in these patients. This dose is effective in lowering blood pressure and appears to be suitable for patients with renal function impairment.

The blunting of the antiproteinuric efficacy of ACE inhibition by high sodium intake can be restored by hydrochlorothiazide.

BACKGROUND: Dietary sodium restriction enhances the antiproteinuric and blood pressure lowering effect of ACE inhibition. In clinical practice, however, long-term compliance to a low-sodium diet may be difficult to obtain. We therefore investigated whether the blunting of the antiproteinuric and blood pressure lowering efficacy of ACE inhibition by high sodium intake can be restored by the addition of a diuretic. PATIENTS AND METHODS: Seven proteinuric patients with non-diabetic renal disease on chronic ACE inhibition were studied during three consecutive 4-week periods: low sodium (50 mmol/day), high sodium (200 mmol/day) and high sodium plus hydrochlorothiazide (50 mg o.i.d.). RESULTS: During low sodium intake proteinuria was 3.1 (0.7-5.2) g/day, during high sodium intake proteinuria increased to 4.5 (1.6-9.2) g/day (P < 0.05). Interestingly, addition of hydrochlorothiazide again reduced proteinuria to 2.8 (0.6-5.8) g/day (P < 0.05). Mean arterial blood pressure was 89 (84-96), 98 (91-104) and 89 (83-94) mmHg (P < 0.05) during the three periods, respectively. CONCLUSION: Addition of hydrochlorothiazide can overcome the blunting of the therapeutic efficacy of ACE inhibition on proteinuria and blood pressure by a high sodium intake.

Is the antiproteinuric response to inhibition of the renin-angiotensin system less effective during the night?

BACKGROUND: In glomerular disease proteinuria usually has a circadian pattern with maximum excretion during the day. Blockade of the renin-angiotensin system (RAS) results in a 50% reduction of proteinuria as measured in 24-h urine collections. We questioned whether anti-proteinuric treatment by blockade of the RAS is as effective during the day as during the night. METHODS: We analysed data from two intervention studies on proteinuria in patients with non-diabetic renal disease. In the first study, six hospitalized patients (proteinuria 5.8 +/- 2.9 g/day) were treated with the renin-inhibitor remikiren 600 mg o.d. during 8 days. In the second study eight ambulant patients (proteinuria 7.5 +/- 2.7 g/day) were treated during 6 weeks with the ACE-inhibitor trandolapril 4 mg o.d. Urine was collected in a day- and in a night-time portion. RESULTS: Daytime proteinuria declined from 0.29 +/- 0.15 to 0.22 +/- 0.11 g/h (P < 0.05) during remikiren and from 0.33 +/- 0.14 to 0.16 +/- 0.08 g/h (P < 0.05) during trandolapril. Night-time proteinuria, however, was not significantly reduced from 0.23 +/- 0.11 to 0.19 +/- 0.11 g/h during remikiren and from 0.29 +/- 0.17 to 0.20 +/- 0.12 g/h during trandolapril. Both interventions effectively lowered blood pressure during the day as well as the night. CONCLUSION: In both studies relative nocturnal therapy resistance to the antiproteinuric effect of RAS blockade was found, despite 24-h efficacy of blood pressure effect. This may have clinical relevance because it contributes to rest-proteinuria and thus may affect long term renal function outcome. It may be worthwhile to explore alternative therapeutic regimens to improve the nocturnal antiproteinuric response.

Renal hemodynamic effects of candesartan in normal and impaired renal function in humans.

The effects of angiotensin II type I receptor antagonist candesartan cilexitil, 8 mg once daily, were studied after single dose and after five days treatment in 17 hypertensive patients [median mean arterial pressure (MAP) 118 mm Hg, range 84 to 134] with renal function impairment of different severity [glomerular filtration rate (GFR) 60 ml/min, range 11 to 161]. The MAP fell by -8% (-14 to -5) and -11 (-16 to -5)% after single and multiple dose, respectively (both P < 0.02). Effective renal plasma flow (ERPF) increased by 13% (7 to 19) and 10% (3 to 14) after single and multiple dose, respectively (both P < 0.02), while the GFR did not change. Filtration fraction (FF) fell by -11% (-14 to -5) and -12% (-13 to -4) after single and multiple doses, respectively (both P < 0.02). After a single dose the % change in ERPF (r = 0.58) and FF (r = -0.52, both P < 0.05) positively correlated with pretreatment GFR, indicating a more pronounced response in patients with normal GFR. After five days of treatment these correlations were absent, indicating similar renal vasodilation in patients with normal and impaired renal function. Thus, multiple dose candesartan cilexitil had a favorable renal hemodynamic profile, irrespective of pretreatment renal function. Further studies are needed to establish whether this provides long-term renoprotection as well.

The timing of maternity in the Netherlands.

"In this paper the timing of maternity is estimated by a hazard model. The novel aspect of this paper is that it is shown that wages and total household labor income have a significant effect on the timing of maternity. Both the wage rate of the woman and the wage rate of the husband have a negative effect on the timing of maternity. Total household labor income increases the probability of having a child at an earlier age.... Women working in the labor market delay the timing of maternity compared to non-participating women. Attending school has the same effect. Until the age of 28 the maternity hazard increases with age, after that it decreases." Data are from a longitudinal survey of 4,020 men and women in the Netherlands who were interviewed during the period 1980-1985.

A device for the location and protection of the recurrent laryngeal nerve during operations upon the neck.

A new locating system by stimulus-movement-registration of the recurrent laryngeal nerve during neck operations was applied safely and successfully in six instances. In our opinion, the principle of stimulus-movement-registration deserves wide application in neck operations, as it is simple, reliable and safe and may obviate accidental damage to the recurrent laryngeal nerve.