Early Vasopressor Research Articles

Fluids and sepsis: changing the paradigm of fluid therapy: a case report

BackgroundOver the past 16 years, sepsis management has been guided by large-volume fluid administration to achieve certain hemodynamic optimization as advocated in the Rivers protocol. However, the safety of such practice has been questioned because large-volume fluid administration is associated with fluid overload and carries the worst outcome in patients with sepsis. Researchers in multiple studies have declared that using less fluid leads to increased survival, but they did not describe how to administer fluids in a timely and appropriate manner.Case presentationAn 86-year-old previously healthy Sundanese man was admitted to the intensive care unit at our institution with septic shock, acute kidney injury, and respiratory distress. Standard care was implemented during his initial care in the high-care unit; nevertheless, his condition worsened, and he was transferred to the intensive care unit. We describe the timing of fluid administration and elaborate on the amount of fluids needed using a conservative fluid regimen in a continuum of resuscitated sepsis.ConclusionsBecause fluid depletion in septic shock is caused by capillary leak and pathologic vasoplegia, continuation of fluid administration will drive intravascular fluid into the interstitial space, thereby producing marked tissue edema and disrupting vital oxygenation. Thus, fluids have the power to heal or kill. Therefore, management of patients with sepsis should entail early vasopressors with adequate fluid resuscitation followed by a conservative fluid regimen.

Abstract 319: Development and Validation of a Mortality Prediction Model for Hospitalized Heart Failure Patients

Background: Clinical predication models for hospitalized patients with heart failure have good performance characteristics but require medical record review, which is both costly and time-consuming. In contrast, administrative claims data are readily available for research but have limited clinical detail. Methods: We used highly detailed billing data to derive a multivariable in-hospital mortality prediction model for patients with heart failure. We validated the model in a separate multi-hospital dataset derived from electronic health record (EHR) data. For the derivation, we included patients aged ≥18 years admitted to one of 433 hospitals that participate in the Premier, Inc. Data Warehouse (PDW) between January 2009 and June 2011. Patients with a principal ICD-9-CM diagnosis of heart failure or principal diagnosis of respiratory failure with secondary diagnosis of heart failure were included. After dividing the dataset into derivation and validation sets, we used generalized estimating equations to estimate the parameters of a generalized linear model that adjusted for clustering within hospitals. The model included selected patient demographics, comorbidities, history of prior heart failure admissions, and initial medications and therapies (e.g., inotropes, mechanical ventilation) administered in the first 2 hospital days. We applied the models to the validation set. Finally, we applied the coefficients from the model to a novel multi-hospital dataset, HealthFacts (Cerner Corp), which contains information about hospitalizations and is derived from the electronic health record of 76 participating sites (years 2010-2012). Results: In PDW, we identified 200,832 patients ≥18 years old with a diagnosis of heart failure. Of these, 80% (160,839) were randomly assigned to the derivation cohort and the remaining 20% (39,993) were assigned to the validation cohort. Mortality was 4.0%. In the derivation cohort, the model showed a c-statistic of 0.79 Factors that were most strongly associated with mortality included age over 80 years, early inotropes, early vasopressors, and diagnosis of acute kidney injury that was present on admission. In the validation cohort, the c-statistic was 0.79. We then validated the model in the HealthFacts dataset, which had a higher percentage of African American patients (28% vs. 17%). In this cohort, the c-statistic was 0.82. Conclusions: A heart failure mortality model based on detailed administrative data available in the first 2 hospital days had excellent performance characteristics in a derivation and an external, EHR-based validation dataset. When clinical data are not available, this model may be useful for severity adjustment in comparative effectiveness studies of heart failure patients.

Fluid resuscitation and vasopressors in severe trauma patients.

To discuss the fluid resuscitation and the vasopressor support in severe trauma patients. A critical point is to prevent a potential increase in bleeding by an overly aggressive resuscitative strategy. Indeed, large-volume fluid replacement may promote coagulopathy by diluting coagulation factors. Moreover, an excessive level of mean arterial pressure may induce bleeding by preventing clot formation. Fluid resuscitation is the first-line therapy to restore intravascular volume and to prevent cardiac arrest. Thus, fluid resuscitation before bleeding control must be limited to the bare minimum to maintain arterial pressure to minimize dilution of coagulation factors and complications of over fluid resuscitation. However, a strategy of low fluid resuscitation needs to be handled in a flexible way and to be balanced considering the severity of the hemorrhage and the transport time. A target systolic arterial pressure of 80-90 mmHg is recommended until the control of hemorrhage in trauma patients without brain injury. In addition to fluid resuscitation, early vasopressor support may be required to restore arterial pressure and prevent excessive fluid resuscitation. It is crucial to find the best alchemy between fluid resuscitation and vasopressors, to consider hemodynamic monitoring and to establish trauma resuscitative protocols.

Vasopressor Use during Emergency Trauma Surgery

Most evidence suggests early vasopressor use is associated with death after trauma, but no previous study has focused on patients requiring emergency operative intervention (OR). We test the hypothesis that vasopressors are harmful in this population. Records from 746 patients requiring OR from July 2009 to March 2013 were retrospectively reviewed and stratified based on vasopressor use (epinephrine [EPI], phenylephrine, ephedrine, norepinephrine, dobutamine, vasopressin) or no vasopressor use. Vasopressors were administered to 225 patients (30%) during OR; 59 patients (8%) received multiple vasopressors. Patients who received vasopressors were older, more severely injured, had worse vital signs, and increased mortality rate (all P < 0.001). EPI was independently associated with mortality (odds ratio, 6.88; P = 0.001). If patients who received EPI were excluded, there was no difference in mortality between those who received vasopressors alone or in combination and those that did not (5 vs 6%, P = 0.523), although multiple markers of injury severity were worse. We conclude that vasopressor use is relatively common in the most severely injured patients requiring OR and is associated with mortality. EPI is most often used for cardiac arrest, whereas other vasopressors are used for their vasoconstrictive properties. This suggests that, except for EPI, vasopressors during OR are not independently associated with mortality.

Coefficient of Variation of Coarsely Sampled Heart Rate is Associated With Early Vasopressor Independence in Severe Sepsis and Septic Shock

To determine whether variability of coarsely sampled heart rate and blood pressure early in the course of severe sepsis and septic shock predicts successful resuscitation, defined as vasopressor independence at 24 hours after admission. In an observational study of patients admitted with severe sepsis or septic shock from 2009 to 2011 to either of 2 intensive care units (ICUs) at a tertiary-care hospital, in whom blood pressure was measured via an arterial catheter, we sampled heart rate and blood pressure every 30 seconds over the first 6 hours of ICU admission and calculated the coefficient of variability of those measurements. Primary outcome was vasopressor independence at 24 hours; and secondary outcome was 28-day mortality. We studied 165 patients, of which 97 (59%) achieved vasopressor independence at 24 hours. Overall, 28-day mortality was 15%. Significant predictors of vasopressor independence at 24 hours included the coefficient of variation of heart rate, age, Acute Physiology and Chronic Health Evaluation II, the number of increases in vasopressor dose, mean vasopressin dose, mean blood pressure, and time-pressure integral of mean blood pressure less than 60 mm Hg. Lower sampling frequencies (up to once every 5 minutes) did not affect the findings. Increased variability of coarsely sampled heart rate was associated with vasopressor independence at 24 hours after controlling for possible confounders. Sampling frequencies of once in 5 minutes may be similar to once in 30 seconds.

Myocardial stunning after resuscitation from cardiac arrest following spinal anaesthesia.

Cardiac arrest associated with spinal anaesthesia has been well researched. Myocardial stunning after successful resuscitation from cardiac arrest is seen in up to 2/3rd of in-hospital cardiac arrests. Myocardial stunning after resuscitation from cardiac arrest associated with spinal anaesthesia has probably not been reported earlier. Our case, an ASA physical status I lady, posted for tubal reanastomosis surgery developed bradycardia followed by asystole, approximately 5 minutes after giving subarachnoid block. Return of spontaneous circulation (ROSC) was achieved within 2 minutes with cardiopulmonary resuscitation (CPR) and defibrillation for pulseless ventricular tachycardia. Patient developed delayed pulmonary oedema, which was probably due to myocardial stunning. In the present case, inadequate preloading could have precipitated bradycardia progressing to cardiac arrest which, after resuscitation led to reversible myocardial dysfunction. We conclude that early vasopressor infusion, titrated fluids and echocardiography should be considered in immediate post cardiac arrest phase following spinal anaesthesia.

TAP block - or general anaesthesia?

Whilst I would agree that transversus abdominis plane (TAP) block as the sole method of anaesthesia for hip hemiarthroplasty is worthy of further research, I would suggest that Stuart-Smith's patient effectively received general anaesthesia, augmented by TAP block 1. Reliable regional anaesthesia for hip hemiarthroplasty requires not only that the sensory innervation of the peri-incisional skin, subcutaneous tissues and muscle is blocked, but also that of the hip joint and capsule, including branches of the sacral plexus which supply the posteroinferior aspects of the capsule 2. Whilst Stuart-Smith is correct in noting that high-volume TAP blocks can extend caudad beyond L1 to involve the sacral plexus, the patient described was only assessed as having loss of pain and cold sensation as far caudad as L3, suggesting sensation may have been retained below this level. Peri-operatively, the patient received a relatively high-dose infusion of propofol (6.4 mg.kg−1.h−1) for sedation during surgery, in addition to the 2 mg midazolam and 20 mg ketamine administered before TAP block insertion. Outwith the co-administration of midazolam and ketamine, the Summary of Product Characteristics for propofol states that general anaesthesia can usually be maintained using rates of infusion “in the region of 4–12 mg.kg−1.h−1” and that “maintenance of sedation … (for) most (adult) patients will require 1.5–4.5 mg.kg−1.h−1’, although in elderly patients ‘the rate of infusion … should … be reduced. Patients of ASA grades 3 and 4 will require further reductions in dose and dose rate” 3, hence my assertion that the patient effectively received general anaesthesia. As Sieber et al. have noted, general anaesthesia occurs frequently in elderly patients during propofol-based sedation 4. Furthermore, anaesthesia is an important element of the prehabilitative continuum that aims to return hip fracture patients seamlessly to their pre-fracture functional status. Compared with light sedation (1.9 mg.kg−1.h−1) in elderly patients undergoing hip fracture under spinal anaesthesia, heavy sedation (6.6 mg.kg−1.h−1) increases the risk of postoperative delirium, which in turn is associated with poor functional recovery after surgery 5. Finally, I do not agree with Stuart-Smith's justification for avoiding spinal anaesthesia in favour of TAP block in the first instance, namely that the former ‘might result in dangerous levels of hypotension’. Even given the procedural difficulties assessing the patient's left ventricular function echocardiographically, the administration of low-dose, unilateral intrathecal anaesthesia (< 1.5 ml hyperbaric bupivacaine 0.5%) is associated with only small (< 20%) mean reductions in systolic blood pressure 6, and may have reduced left ventricular work by reducing ventricular preload through arteriolar vasodilation. The pre-induction insertion of a radial arterial line would have facilitated beat-to-beat diagnosis of hypotension, enabling early vasopressor intervention. Use of TAP blockade during the repair of hip fractures is very intriguing, and I would encourage Stuart-Smith to conduct further research formally assessing the reliability of motor and sensory blockade of the hip together with bispectral index-guided propofol sedation, in order to assess the utility of this method as an alternative to intrathecal anaesthesia for frail, elderly patients with hip fracture.

Does vasopressor therapy have an indication in hemorrhagic shock?

This review aimed to answer whether the vasopressors are useful at the early phase of hemorrhagic shock. Data were taken from published experimental studies and clinical trials. Published case reports were discarded. A search of electronic database PubMed was conducted using keywords of hemorrhagic shock, vasopressors, vasoconstrictors, norepinephrine, epinephrine, vasopressin. The redundant papers were not included. We identified 15 experimental studies that compared hemorrhagic shock resuscitated with or without vasopressors, three retrospective clinical studies, and one controlled trial. The experimental and clinical studies are discussed in the clinical context, and their strengths as well as limitations are highlighted. There is a strong rationale for a vasopressor support in severe hemorrhagic shock. However, this should be tempered by the risk of excessive vasoconstriction during such hypovolemic state. The experimental models must be analyzed within their own limits and cannot be directly translated into clinical practice. In addition, because of many biases, the results of clinical trials are debatable. Therefore, based on current information, further clinical trials comparing early vasopressor support plus fluid resuscitation versus fluid resuscitation alone are warranted.

Coefficient of variation of coarsely sampled heart rate predicts early vasopressor independence in early severe sepsis and septic shock

Coefficient of variation of coarsely sampled heart rate predicts early vasopressor independence in early severe sepsis and septic shock

Early Vasopressor Use in Critical Injury Is Associated With Mortality Independent From Volume Status

Early Vasopressor Use in Critical Injury Is Associated With Mortality Independent From Volume Status

Early Vasopressor Use in Critical Injury Is Associated With Mortality Independent From Volume Status

Complications of excessive crystalloid after critical injury have increased interest in vasopressor support. However, it is hypothesized that vasopressor use in patients who are under-resuscitated is associated with death. We performed this study to determine whether volume status is associated with increased mortality in the critically injured exposed to early vasopressors. The intensive care unit database at a Level I center was queried for all adult admissions surviving for >24 hours from January 1, 2001, to December 31, 2008. Patients with spinal cord injury and severe traumatic brain injury were excluded. The vasopressor group [Vaso (+)] was exposed to dopamine, epinephrine, phenylephrine, norepinephrine, or arginine vasopressin within 24 hours of admission. Demographic and injury data were studied including intensive care unit admission central venous pressure. Hypovolemia [Hypov (+)] was considered an admission central venous pressure ≤8 mm Hg. The Vaso (+) group was analyzed to determine whether Hypov (+) was independently associated with death. Of 1,349 eligible patients, 26% (351) were Vaso (+). Mortality was 43.6% (153) in the Vaso (+) versus 4.2% (42) in the Vaso (-) group (17.60 [12.10-25.60], <0.01). Vasopressor exposure was associated with death independent of injury severity. In Vaso (+) patients, Hypov (+) was not associated with mortality, whereas Emergency Department admission Glasgow Coma Scale ≤8 and multiple vasopressor use were. Vasopressor exposure early after critical injury is independently associated with death and mortality is increased regardless of fluid status. Although it is not advisable to withhold support with impending cardiovascular collapse, use of any vasopressor during ongoing resuscitation should be approached with extreme caution regardless of volume status.

Early Vasopressors in Trauma Linked to Higher Mortality

Early Vasopressors in Trauma Linked to Higher Mortality

Early Use of Vasopressors After Injury: Caution Before Constriction

Recent evidence suggests that overly aggressive crystalloid resuscitation is associated with poor outcome. This has led to a renewed interest in the use of vasopressors for hemodynamic support during resuscitation after injury. We sought to characterize early vasopressor (EV) use and aggressive early crystalloid resuscitation (ECR) and their association with mortality in severely injured patients. Data were obtained from a multicenter, prospective, cohort study designed to evaluate the outcome of blunt injured adults in hemorrhagic shock. Early deaths (<48 hours) were excluded from the analysis. A single Cox proportional hazard regression model was used to evaluate the effects of EV use (levophed, phenylephrine, dopamine, or vasopressin) and aggressive ECR on mortality at 12 and 24 hours postinjury, while controlling for important physiologic, injury, resuscitation, and patient demographic confounders. Cox proportional hazard regression revealed that EV use within 12 hours after injury was independently associated with over an 80% higher risk of mortality (hazard ratio [HR] 1.81, 95% confidence interval [CI] 1.1-2.9, p = 0.013), and was independently associated with over a twofold higher risk of mortality at 24 hours (HR 2.15, 95% CI 1.4-3.4, p = 0.001). These findings were consistent across all vasopressor subtypes. Aggressive ECR was independently associated with a 40% reduction in mortality (HR 0.594, 95% CI 0.37-0.95, p = 0.030). These findings provide evidence that the early use of vasopressors for hemodynamic support after hemorrhagic shock may be deleterious, and should be used cautiously and not in place of aggressive crystalloid resuscitation after severe blunt injury.

Comparative effects of early versus delayed use of norepinephrine in resuscitated endotoxic shock*

To assess hemodynamic, tissue oxygenation, and tissue perfusion changes by comparing traditional therapy (fluid resuscitation followed by vasopressor treatment) and alternative therapy (early vasopressor treatment) in a hyperkinetic and sedated model of endotoxic shock. Prospective controlled experimental study. Animal research laboratory. Male Wistar rats. Rats were anesthetized, mechanically ventilated, paralyzed, and instrumented to measure mean arterial pressure, heart rate, pulse pressure variation, aortic and mesenteric blood flow, muscle and liver tissue oxygen pressure, blood gas, and lactate. Rats were randomly divided into five groups (n = 7): endotoxin alone (Endo), endotoxin plus norepinephrine (Endo/NE), endotoxin plus fluid therapy alone (ENDO/Fl), endotoxin plus fluid therapy plus late catecholamine (Endo/Fl/Late NE), and endotoxin plus fluid therapy plus simultaneous norepinephrine administration (Endo/Fl/Early NE). Mean arterial pressure increased to baseline values only in the catecholamine-treated group (p < .05). In ENDO/Fl, Endo/Fl/Late NE, and Endo/Fl/Early NE, aortic blood flow was maintained. Mesenteric blood flow was maintained at baseline values only in the catecholamine-treated groups. Mesenteric/aortic blood flow ratio was higher in the early catecholamine group (p < .05). Endo and ENDO/Fl were associated with a marked decrease in liver PO2, which was maintained in catecholamine-treated groups (p < .01). Plasma lactate was lower in the Endo/Fl/Early NE group. Volume resuscitation was higher in Endo and Endo/Fl/Late NE groups with 28 +/- 6 and 27 +/- 4 mL, respectively, when compared with the Endo/Fl/Early NE group (19 +/- 3 mL) (p < .05). The use of norepinephrine was associated with improved mean arterial pressure, sustained aortic and mesenteric blood flow, and better tissue oxygenation when compared with fluid resuscitation alone, irrespective of time of administration. The early use of norepinephrine plus volume expansion was associated with a higher proportion of blood flow redistributed to the mesenteric area, lower lactate levels, and less infused volume. Thus, the early use of norepinephrine is safe and may decrease the need for volume resuscitation.

Recent developments in obstetric regional anesthesia. A review of experiences at the Eppendorf University Hospital

The study investigates changes of anaesthesia practice in obstetric patients of a University Hospital over a six years' period. Between 1993 and 1998 data of 7476 deliveries were collected by the perinatal documentation system of the Obstetric Department and by computerized anaesthesia protocols of the Department of Anesthesiology. Since combined spinal-epidural anaesthesia with sufentanil was introduced in 1997, all patients with subarachnoid techniques were prospectively examined between 1997 and 1998. While the total number of deliveries decreased over the years, the number of patients undergoing anaesthetic treatment increased continuously. In parallel, the number of patients with regional anaesthesia increased between 1993 and 1998 from 14.3% to 34.8%. The cesarean delivery rate increased from 23.7% to 28.7% with an increasing number of patients receiving regional anaesthesia for cesarean section (1993: 25.3% vs. 1998: 62.1%). The number of emergency cesarean deliveries performed in regional anaesthesia increased to 19.3% in 1998. The number of neonates with an umbilical artery pH below 7.2 decreased from 18% in 1993 to 11% in 1998. The success rate of regional anaesthesia increased from 88.2% in 1993 to 97.5% in 1998. Combined spinal-epidural anaesthesia provided greater pain reduction when compared with epidural anesthesia (VAS -81 +/- 12 vs. -68 +/- 18). Early vasopressor administration resulted in a decrease of hypotension from 40% to 14% in spinal and from 21% to 13% in combined spinal-epidural anaesthesia. The incidence of postdural puncture headache after subarachnoid anaesthesia was 2.4%. Epidural and subarachnoid application of sufentanil appears to enhance the success rate of obstetric regional anaesthesia. Subarachnoid techniques such as spinal or combined spinal-epidural anaesthesia showed a high effectiveness, low incidence of side effects and high degree of patients' satisfaction.

Reevaluation of the treatment of shock secondary to cardiac infarction.

When given early vasopressor drugs can be an effective from of therapy for cardiogenic shock because they increase coronary blood flow, cardiac output and blood pressure. They vasodilate the coronary vascular bed and in 40 percent of the experiments, reduce total peripheral vascular resistance. The use of 3-hydroxytyramine and the vasopressor-vasodilator combination provide most effective coronary and regional perfusion to other vital organs. New mechanical circulatory assistance techniques applied to the treatment of irreversible cardiogenic shock promise that the high mortality rate associated with this dreaded complication will be reduced.