Haemodynamic assessment and management of hypotension in the preterm.

The management of low blood flow states in premature neonates is fraught with many challenges. We remain over-reliant on regimented stepwise protocols that use mean blood pressure as a threshold for intervention to guide treatment, without giving due consideration to the underlying pathophysiology. The current available evidence does not reflect the need to concentrate on the unique pathophysiology of the preterm infant and thus leads to widespread misuse of vasoactive agents that often do not provide the desired clinical effect. Therefore, understanding the underlying pathophysiological underpinnings of haemodynamic compromise may better guide choice of agent and assess physiological response to the selected intervention.

Assessment of microcirculatory function during hemodialysis.

PURPOSE OF REVIEW: Patients with chronic kidney disease characteristically exhibit microcirculatory dysfunction, in combination with vascular damage. Hemodialysis superimposes additional circulatory stress to the microvasculature (repetitive ischemic insults/cumulative damage) resulting in high mortality. Intradialytic monitoring and hemodialysis delivery is currently limited to macrovascular/systemic assessment and detection of intradialytic systemic hypotension. Monitoring of the microcirculation has the potential to provide valuable information on hemodialysis-induced circulatory stress likely to result in end-organ ischemia (with/without systemic hypotension) generating an opportunity to intervene before tissue injury occurs. RECENT FINDINGS: Various noninvasive technologies have been used assessing the microcirculation in hemodialysis patients at rest. Some technologies have also been applied during hemodialysis studying the effects of treatment on the microcirculation. Despite the approach used, results are consistent. Hemodialysis patients have impaired microcirculations with treatment adding additional stress to inadequately regulated vascular beds. Utility/practicality/clinical relevance vary significantly between methodologies. SUMMARY: Intradialytic monitoring of the microcirculation can provide additional insights into a patient's individual response to treatment. However, this valuable perspective has not been adopted into clinical practice. A microcirculatory view could provide a window of opportunity to enable a precision medicine approach to treatment delivery improving current woefully poor subjective and objective clinical outcomes.

COMBED: Rapid non-invasive Cardiac Output Monitoring Baseline assessment in adult Emergency Department patients with haemodynamic instability.

OBJECTIVE: The application of rapid, non-operator-dependent, non-invasive cardiac output monitoring (COM) may provide early physiological information in ED patients with haemodynamic instability (HI). Our primary objective was to assess the feasibility of measuring pre-intervention (baseline) cardiac index (CI) and associated haemodynamic parameters. METHODS: We performed a prospective observational study of adults shortly after presentation to the ED of a large university hospital with tachycardia or hypotension or both. We applied non-invasive COM for 5 min and recorded CI, mean arterial pressure (MAP), stroke volume index (SVI) and systemic vascular resistance index (SVRI). We assessed for differences between those presenting with hypotension or hypotension and tachycardia with tachycardia alone and between those with or without suspected infection. RESULTS: We obtained haemodynamic parameters in 46 of 49 patients. In patients with hypotension or hypotension and tachycardia (n = 15) rather than tachycardia alone (n = 31), we observed a lower MAP (60.8 vs 87.7, P < 0.0001), CI (2.8 vs 3.9, P = 0.0167) and heart rate (85.5 vs 115.4, P < 0.0001). There was no difference in SVI (33.7 vs 33.4, P = 0.93) or SVRI (1970 vs 2088, P = 0.67). Patients with suspected infection had similar haemodynamic values except for a lower SVRI (1706 vs 2237, P = 0.011). CONCLUSIONS: Rapid, non-operator-dependent, non-invasive COM was possible in >90% of ED patients presenting with HI. Compared with tachycardia alone, patients with hypotension had lower CI, MAP and heart rate, while those with suspected infection had a lower SVRI. This technology provides novel insights into the early state of the circulation in ED patients with HI.

Failure to detect ward hypoxaemia and hypotension: contributions of insufficient assessment frequency and patient arousal during nursing assessments.

BACKGROUND: Postoperative hypotension and hypoxaemia are common and often unrecognised. With intermittent nursing vital signs, hypotensive or hypoxaemic episodes might be missed because they occur between scheduled measurements, or because the process of taking vital signs arouses patients and temporarily improves arterial blood pressure and ventilation. We therefore estimated the fraction of desaturation and hypotension episodes that did not overlap nursing assessments and would therefore usually be missed. We also evaluated the effect of taking vital signs on blood pressure and oxygen saturation. METHODS: We estimated the fraction of desaturated episodes (arterial oxygen saturation <90% for at least 90% of the time within 30 continuous minutes) and hypotensive episodes (MAP <70 mm Hg for 15 continuous minutes) that did not overlap nursing assessments in patients recovering from noncardiac surgery. We also evaluated changes over time before and after nursing visits. RESULTS: Among 782 patients, we identified 878 hypotensive episodes and 2893 desaturation episodes, of which 79% of the hypotensive episodes and 82% of the desaturation episodes did not occur within 10 min of a nursing assessment and would therefore usually be missed. Mean BP and oxygen saturation did not improve by clinically meaningful amounts during nursing vital sign assessments. CONCLUSIONS: Hypotensive and desaturation episodes are mostly missed because vital sign assessments on surgical wards are sparse, rather than being falsely negative because the assessment process itself increases blood pressure and oxygen saturation. Continuous vital sign monitoring will detect more disturbances, potentially giving clinicians time to intervene before critical events occur.

Best practices for safe use of SGLT-2 inhibitors developed from an expert panel Delphi consensus process.

PURPOSE: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors have demonstrated glycemic efficacy and cardiovascular and renal benefits in people with type 2 diabetes mellitus (T2DM). However, they are also associated with serious adverse events (AEs), but little consensus exists for clinicians regarding AE management. This study aimed to develop a list of best practices for the safe use and monitoring of SGLT-2 inhibitors in people with T2DM. METHODS: A 15-member interprofessional panel was surveyed in a four-round Delphi process. Panelists were asked to comment on and rank statements regarding initial prescribing considerations and actions for minimizing and managing eight specific AEs and a broad category for other AEs. In the final round, panelists selected if the statements should be considered a best practice specific to SGLT-2 inhibitors, a best practice for general safe medication use in T2DM, or if the statement should not be considered as a best practice for safe medication use. RESULTS: Consensus was achieved for 36 best practice statements specific to SGLT-2 inhibitors and 24 statements as general best practices for safe medication use. Fifty-six percent of the best practice statements for SGLT-2 inhibitors related to managing and/or preventing hypotension, urinary tract infections, and genital infections. The general best practices for safe medication use primarily focused on medication histories, past medical history considerations, physical exam components, and patient education. CONCLUSION: A list of best practice statements was developed using the Delphi method, which can be utilized by clinicians to guide the safe use and monitoring of SGLT-2 inhibitors in people with T2DM.

Hospital costs associated with intraoperative hypotension among non-cardiac surgical patients in the US: a simulation model.

Objective: Recent studies indicate intraoperative hypotension, common in non-cardiac surgical patients, is associated with myocardial injury, acute kidney injury, and mortality. This study extends on these findings by quantifying the association between intraoperative hypotension and hospital expenditures in the US. Methods: Monte Carlo simulations (10,000 trial per simulation) based on current epidemiological and cost outcomes literature were developed for both acute kidney injury (AKI) and myocardial injury in non-cardiac surgery (MINS). For AKI, three models with different epidemiological assumptions (two models based on observational studies and one model based on a randomized control trial [RCT]) estimate the marginal probability of AKI conditional on intraoperative hypotension status. Similar models are also developed for MINS (except for the RCT case). Marginal probabilities of AKI and MINS sequelae (myocardial infarction, congestive heart failure, stroke, cardiac catheterization, and percutaneous coronary intervention) are multiplied by marginal cost estimates for each outcome to evaluate costs associated with intraoperative hypotension. Results: The unadjusted (adjusted) model found hypotension control lowers the absolute probability of AKI by 2.2% (0.7%). Multiplying these probabilities by the marginal cost of AKI, the unadjusted (adjusted) AKI model estimated a cost reduction of $272 [95% CI = $223-$321] ($86 [95% CI = $47-$127]) per patient. The AKI model based on relative risks from the RCT had a mean cost reduction estimate of $281 (95% CI = -$346-$750). The unadjusted (adjusted) MINS model yielded a cost reduction of $186 [95% CI = $73-$393] ($33 [95% CI = $10-$77]) per patient. Conclusions: The model results suggest improved intraoperative hypotension control in a hospital with an annual volume of 10,000 non-cardiac surgical patients is associated with mean cost reductions ranging from $1.2-$4.6 million per year. Since the magnitude of the RCT mean estimate is similar to the unadjusted observational model, the institutional costs are likely at the upper end of this range.

Gunshot Injuries to the Extremity: Is Immediate General Surgery Presence Needed?

Gunshot wounds (GSW) are becoming increasingly prevalent in urban settings. GSW to the trunk mandate full trauma activation and immediate surgeon response because of the high likelihood of operative intervention. Extremity GSW proximal to the knee/elbow also require full trauma activation based on American College of Surgeons Committee on trauma standards. However, whether isolated extremity GSW require frequent operative intervention is unclear. We evaluated GSW at our Level I trauma center from January 2012 to December 2016. Demographic data and injury patterns were abstracted from the trauma registry and charts. The number of GSW increased yearly but the age, gender, Injury Severity Score and injury pattern did not change (P = ns, not shown). There were 504 GSW that included an extremity and 194 (38%) involved multiple body regions. There were 310 GSW (62%) isolated to an extremity and 176 were proximal to the elbow/knee. If proximal GSW had an Emergency Department systolic blood pressure <90 mm Hg, 53 per cent underwent vascular repair, 12 per cent had soft tissue repair, and 29 per cent required no operation. If proximal GSW had an Emergency Department blood pressure >90 mm Hg, 57 per cent underwent orthopedic repair, 22 per cent required no surgery, and only 13 per cent required vascular repair (P < 0.01). In the absence of other criteria for full trauma activation such as shock, the need for the immediate presence of a general surgeon to perform emergency surgery for a GSW isolated to the extremity is low.

Assessment of dynamic variables of fluid responsiveness to predict desufflation-induced hypotension during paediatric laparoscopic surgery.

BACKGROUND: During laparoscopic surgery in paediatric patients, sudden hypotension may occur following peritoneal desufflation due to hypovolaemia or an acute increase in gastrointestinal venous capacitance by the release of intra-abdominal pressure. This study examined whether dynamic variables of fluid responsiveness during pneumoperitoneum can predict the occurrence of hypotension following desufflation. METHODS: A total of 120 paediatric subjects were prospectively enrolled. A predictor was derived from the initial 83 subjects and validated thereafter in 37 high-risk subjects. The pleth variability index, respiratory variation in the pulse oximetry plethysmographic waveform (ΔPOP), systolic pressure variation and pulse pressure variation during pneumoperitoneum were obtained 1 min before desufflation. Predictors of desufflation-induced hypotension were investigated using the multivariable logistic regression analysis. Predictability was assessed using the area under the receiver-operating characteristic curve (AUC). RESULTS: In the derivation cohort, 27% (n=23) of subjects developed hypotension. Only ΔPOP was found to be a predictor, and showed high predictability of desufflation-induced hypotension [AUC 0.87, P<0.0001, 95% confidence interval (CI): 0.78-0.93]. A ΔPOP cut-off point of 38% predicted hypotension with a sensitivity of 83% and a specificity of 90%. In the validation cohort, 43% (n=16) of subjects developed hypotension, and ΔPOP was verified to be highly predictive of the occurrence of hypotension (AUC 0.90, P<0.0001, 95% CI: 0.76-0.98). The sensitivity and specificity of a ΔPOP cut-off point of 38% to predict hypotension was 88% and 90%, respectively. CONCLUSIONS: The ΔPOP during pneumoperitoneum is useful in predicting desufflation-induced hypotension during paediatric laparoscopic surgery. CLINICAL TRIAL REGISTRATION: NCT02536521.

Hemodynamic Assessment and Monitoring of Premature Infants.

The management of the hemodynamic status of critically ill preterm infants, particularly around the periviable period, remains a significant challenge in the neonatal intensive care unit for a multitude of reasons. The causes of hemodynamic compromise in this population are heterogeneous and usually superimposed on the complex physiologic processes that occur during transition from fetal to neonatal life. This review outlines the unique nature of low blood flow states in this population and present an overview of the current methods for identification and assessment of hemodynamic compromise.

Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).

IMPORTANCE: The Third International Consensus Definitions Task Force defined sepsis as "life-threatening organ dysfunction due to a dysregulated host response to infection." The performance of clinical criteria for this sepsis definition is unknown. OBJECTIVE: To evaluate the validity of clinical criteria to identify patients with suspected infection who are at risk of sepsis. DESIGN, SETTINGS, AND POPULATION: Among 1.3 million electronic health record encounters from January 1, 2010, to December 31, 2012, at 12 hospitals in southwestern Pennsylvania, we identified those with suspected infection in whom to compare criteria. Confirmatory analyses were performed in 4 data sets of 706,399 out-of-hospital and hospital encounters at 165 US and non-US hospitals ranging from January 1, 2008, until December 31, 2013. EXPOSURES: Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score, systemic inflammatory response syndrome (SIRS) criteria, Logistic Organ Dysfunction System (LODS) score, and a new model derived using multivariable logistic regression in a split sample, the quick Sequential [Sepsis-related] Organ Failure Assessment (qSOFA) score (range, 0-3 points, with 1 point each for systolic hypotension [≤100 mm Hg], tachypnea [≥22/min], or altered mentation). MAIN OUTCOMES AND MEASURES: For construct validity, pairwise agreement was assessed. For predictive validity, the discrimination for outcomes (primary: in-hospital mortality; secondary: in-hospital mortality or intensive care unit [ICU] length of stay ≥3 days) more common in sepsis than uncomplicated infection was determined. Results were expressed as the fold change in outcome over deciles of baseline risk of death and area under the receiver operating characteristic curve (AUROC). RESULTS: In the primary cohort, 148,907 encounters had suspected infection (n = 74,453 derivation; n = 74,454 validation), of whom 6347 (4%) died. Among ICU encounters in the validation cohort (n = 7932 with suspected infection, of whom 1289 [16%] died), the predictive validity for in-hospital mortality was lower for SIRS (AUROC = 0.64; 95% CI, 0.62-0.66) and qSOFA (AUROC = 0.66; 95% CI, 0.64-0.68) vs SOFA (AUROC = 0.74; 95% CI, 0.73-0.76; P < .001 for both) or LODS (AUROC = 0.75; 95% CI, 0.73-0.76; P < .001 for both). Among non-ICU encounters in the validation cohort (n = 66 522 with suspected infection, of whom 1886 [3%] died), qSOFA had predictive validity (AUROC = 0.81; 95% CI, 0.80-0.82) that was greater than SOFA (AUROC = 0.79; 95% CI, 0.78-0.80; P < .001) and SIRS (AUROC = 0.76; 95% CI, 0.75-0.77; P < .001). Relative to qSOFA scores lower than 2, encounters with qSOFA scores of 2 or higher had a 3- to 14-fold increase in hospital mortality across baseline risk deciles. Findings were similar in external data sets and for the secondary outcome. CONCLUSIONS AND RELEVANCE: Among ICU encounters with suspected infection, the predictive validity for in-hospital mortality of SOFA was not significantly different than the more complex LODS but was statistically greater than SIRS and qSOFA, supporting its use in clinical criteria for sepsis. Among encounters with suspected infection outside of the ICU, the predictive validity for in-hospital mortality of qSOFA was statistically greater than SOFA and SIRS, supporting its use as a prompt to consider possible sepsis.

Hemodialysis in children with ventriculoperitoneal shunts: prevalence, management and outcomes.

BACKGROUND: Hemodialysis (HD) in children with a concomitant ventriculoperitoneal shunt (VPS) is rare. Registry data suggest that peritoneal dialysis with a VPS is safe, but little is known about HD in the presence of a VPS. METHODS: We performed a 10-year survey to determine the prevalence of a VPS, complications and outcome in children with a VPS on HD in 15 dialysis units from the 13 countries participating in the European Pediatric Dialysis Working Group. RESULTS: Eleven cases of HD with a VPS were reported (prevalence 1.33 %; 328 patient-months) and compared with prospective Registry data. The median age at start of dialysis was 9.6 [inter-quartile range (IQR) 1.0-15.0] years and median HD vintage was 2.4 (IQR 1.7-3.0) years. Dialysis was performed through a central venous line (CVL) and through an arteriovenous fistula in six and five children, respectively. Three CVL infections occurred in two children, but these children did not develop VPS infections or meningitis. Symptoms of hemodynamic instability were reported in six (55 %) children at least once per week, with hypotension or hypertension occurring in four of these children and nausea, vomiting and headaches occurring in two; four other children reported less frequent symptoms. Seizures on dialysis occurred in two children, at a frequency of less than once per month, with one child also experiencing visual disturbances. During follow-up (median 4.0; IQR 0.38-7.63 years), three children remained on HD and eight had a functioning transplant. No patients were switched to PD. CONCLUSIONS: Hemodialysis in children with a VPS is safe, but associated with frequent symptoms of hemodynamic instability. No episodes of VPS infection or meningitis were seen among the children in the survey, not even in those with CVL sepsis.

An abdominal computed tomography may be safe in selected hypotensive trauma patients with positive Focused Assessment with Sonography in Trauma examination.

BACKGROUND: Positive Focused Assessment with Sonography in Trauma examination and hypotension often indicate urgent surgery. An abdomen/pelvis computed tomography (apCT) may allow less invasive management but the delay may be associated with adverse outcomes. METHODS: Patients in the Prospective Observational Multicenter Major Trauma Transfusion study with hypotension and a positive Focused Assessment with Sonography in Trauma (HF+) examination who underwent a CT (apCT+) were compared with those who did not. RESULTS: Of the 92 HF+ identified, 32 (35%) underwent apCT during initial evaluation and apCT was associated with decreased odds of an emergency operation (odds ratio .11, 95% confidence interval .001 to .116) and increased odds of angiographic intervention (odds ratio 14.3, 95% confidence interval 1.5 to 135). There was no significant difference in 30-day mortality or need for dialysis. CONCLUSIONS: An apCT in HF+ patients is associated with reduced odds of emergency surgery, but not mortality. Select HF+ patients can safely undergo apCT to obtain clinically useful information.

Refined assessment of blood pressure instability after spinal cord injury.

BACKGROUND: This study determined whether the Autonomic Dysfunction Following Spinal Cord Injury (ADFSCI) questionnaire, a measure of self-reported frequency and severity of symptoms during hypo- and hypertensive episodes, correlates with blood pressure (BP) instability. In addition, test-retest reliability of the ADFSCI questionnaire was assessed. METHODS: Thirty individuals with spinal cord injury (SCI) (aged 42±12 years; level of lesion = C3-L1; American Spinal Injury Association Impairment Scale = A-C; lesion duration = 1 month to 30 years after injury) participated in this study. Twenty-four-hour ambulatory BP monitoring (ABPM) was used to assess BP instability. ABPM recorded systolic BP (SBP), diastolic BP (DBP), and heart rate at 15-minute intervals during the daytime and 1-hour intervals during the nighttime. Test-retest reliability was performed by completion of the ADFSCI questionnaire on 2 occasions (i.e., 9±4 days in between). RESULTS: Individuals with SCI who self-reported autonomic dysreflexia (AD) episodes showed significantly higher SBP coefficient of variation (CV) (14%) and more AD events (n = 11) than individuals who reported never having AD symptoms (CV = 9%; AD events = 1). Both the number of AD events over the 24-hour period and the BP variability (SBP CV) were significantly related to the patients' self-reported total AD score (rho = 0.522, P = 0.005; rho = 0.584, P = 0.001, respectively) and daily AD frequency (rho = 0.553, P = 0.003; rho = 0.586, P = 0.001, respectively). Conversely, no significant correlations existed between the number of hypotensive events over the 24-hour period and self-reported frequency and severity in the ADFSCI questionnaire. CONCLUSIONS: This study provides evidence that ABPM offers a strong clinical basis for documenting and understanding BP instability, such as AD, and related symptoms in individuals with SCI.

Clinical evaluation compared to the pulse indicator continuous cardiac output system in the hemodynamic assessment of critically ill patients.

OBJECTIVE: The objective was to assess the effects of pulse indicator continuous cardiac output catheterization on the management of critically ill patients and the alteration of therapy in intensive care units. METHODS: One hundred thirty-two patients with primary physiological abnormalities of hypotension or hypoxemia were evaluated. Prior to catheterization, physicians were asked to complete a questionnaire that collected information regarding predictions of the ranges of several hemodynamic variables and plans for therapy. After catheterization, each chart was reviewed by a panel of intensive care attending physicians to determine the possibility of altering the therapy. RESULTS: Overall correct classification of the key variables ranged from 46.0% to 65.4%. Catheterization results prompted alterations in therapy for 45.5% of patients. The fellows were less accurate in predicting hemodynamic values for patients whose diagnoses were unknown, and the primary abnormality was hypotension. There was significant difference in the physicians' abilities to predict the hemodynamics for the subgroups with and without acute myocardial infarction. When the patients were divided into 3 subgroups by Acute Physiology and Chronic Health Evaluation II and Sepsis-related Organ Failure Assessment scores, the fellows had the most difficulty predicting the variables of the moderately ill patients in the middle subgroup, which led to the greatest percentage of therapy alterations for this subgroup; and this difference was significant. CONCLUSIONS: The hemodynamic variables obtained from pulse indicator continuous cardiac output catheterization improved the accuracy of bedside evaluations and led to alterations in therapeutic plans, particularly among the moderately ill patients with hypotension or unknown diagnoses.

Low coronary microcirculatory resistance associated with profound hypotension during intravenous adenosine infusion: implications for the functional assessment of coronary stenoses.

BACKGROUND: Intravenous adenosine infusion produces coronary and systemic vasodilatation, generally leading to systemic hypotension. However, adenosine-induced hypotension during stable hyperemia is heterogeneous, and its relevance to coronary stenoses assessment with fractional flow reserve (FFR) remains largely unknown. METHODS AND RESULTS: FFR, coronary flow reserve, and index of microcirculatory resistance were measured in 93 stenosed arteries (79 patients). Clinical and intracoronary measurements were analyzed among tertiles of the percentage degree of adenosine-induced hypotension, defined as follows: %ΔP(a)=-[100-(hyperemic aortic pressure×100/baseline aortic pressure)]. Overall, %ΔP(a) was -13.6±12.0%. Body mass index was associated with %ΔP(a) (r=0.258; P=0.025) and obesity, an independent predictor of profound adenosine-induced hypotension (tertile 3 of %ΔP(a); odds ratio, 3.95 [95% confidence interval, 1.48-10.54]; P=0.006). %ΔP(a) was associated with index of microcirculatory resistance (ρ=0.311; P=0.002), coronary flow reserve (r=-0.246; P=0.017), and marginally with FFR (r=0.203; P=0.051). However, index of microcirculatory resistance (ß=0.003; P<0.001) and not %ΔP(a) (ß=-0.001; P=0.564) was a predictor of FFR. Compared with tertiles 1 and 2 of %ΔP(a) (n=62 [66.6%]), stenoses assessed during profound adenosine-induced hypotension (n=31 [33.3%]) had lower index of microcirculatory resistance (12.4 [8.6-22.7] versus 20 [15.8-35.5]; P=0.001) and FFR values (0.77±0.13 versus 0.83±0.12; P=0.021), as well as a nonsignificant increase in coronary flow reserve (2.5±1.1 versus 2.2±0.87; P=0.170). CONCLUSIONS: The modification of systemic blood pressure during intravenous adenosine infusion is related to hyperemic microcirculatory resistance in the heart. Profound adenosine-induced hypotension is associated with obesity, lower coronary microcirculatory resistance, and lower FFR values.

[A scale for early assessment of risk of death and myocardial infarction during initial hospitalization of patients with acute coronary syndromes (based on data from the RECORD registry)].

Independent predictors of death and death or myocardial infarction (MI) during initial hospitalization of patients with acute coronary syndromes (ACS) were determined using database of Russian independent ACS registry RECORD. These predictors (admission Killip class II, ST-segment elevation 1 mm, systolic blood pressure 100 mm Hg, hemoglobin <110 g/L, age 65 years, history of diabetes) were attributed equal weight (1 point) and combined in a prognostic scale for assessment of risk of inhospital death and death or MI. The scale did not include markers of necrosis, and the most time consuming component was measurement of hemoglobin. Sensitivity and specificity of risk scores for prediction of death were 78.5%. The use of GRACE score in this group of patients gave similar results. These preliminary data require confirmation on larger populations of patients with ACS.

Definition of hypotension and assessment of hemodynamics in the preterm neonate.

The complexity of postnatal cardiovascular transition has only recently been better appreciated in the very low birth weight neonate. As blood pressure in itself poorly represents systemic blood flow, especially when the fetal channels are open and the developmentally regulated vital organ assignment may not have been completed, efforts to measure systemic blood flow have resulted in a novel, yet incomplete, understanding of the principles and clinical relevance of cardiovascular adaptation during postnatal transition in this patient population. This article describes the definition of hypotension based on the principles of cardiovascular physiology, and reviews the tools available to the clinician and researcher at the bedside to examine the complex relationship among blood pressure, systemic and organ blood flow, and tissue oxygen delivery and oxygen demand in vital and non-vital organs in the very low birth weight neonate. Only after gaining an insight into these complex relationships and processes will we be able to design clinical trials of selected treatment modalities targeting relevant patient sub-populations for the management of neonatal cardiovascular compromise. Only clinical trials based on a solid understanding of developmental cardiovascular physiology tailored to the appropriate patient sub-population hold the promise of being effective and practical, and can lead to improvements in both hemodynamic parameters and clinically relevant outcome measures.

Clinical outcomes according to baseline blood pressure in patients with a low ejection fraction in the CHARM (Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity) Program.

OBJECTIVES: This study sought to investigate the efficacy and tolerability of candesartan, according to baseline blood pressure (BP), in the 4,576 patients with a low ejection fraction (EF) (or=141 mm Hg) and 4 DBP categories (or=81 mm Hg). RESULTS: Low SBP and DBP were associated with worse clinical outcomes. Baseline BP did not modify the effects of candesartan on clinical outcomes: the interaction p value between SBP category and treatment was 0.38 (0.22 for DBP category). For both placebo and candesartan, study drug discontinuation for adverse effects (especially hypotension) was highest in patients in the lowest baseline BP categories. However, the relative risk of discontinuation for hypotension, renal dysfunction, and hyperkalemia in the candesartan compared with placebo group was not increased in patients with a low baseline BP. CONCLUSIONS: In patients with low EF heart failure, the relative risks and benefits of candesartan treatment were similar in patients with a low BP compared to those with a higher BP.