Karthik Raghunathan

Association Between the Choice of IV Crystalloid and In-Hospital Mortality Among Critically Ill Adults With Sepsis*

Objective:Isotonic saline is the most commonly used crystalloid in the ICU, but recent evidence suggests that balanced fluids like Lactated Ringer’s solution may be preferable. We examined the association between choice of crystalloids and in-hospital mortality during the resuscitation of critically ill adults with sepsis. Design:A retrospective cohort study of patients admitted with sepsis, not undergoing any surgical procedures, and treated in an ICU by hospital day 2. We used propensity score matching to control for confounding and compared the following outcomes after resuscitation with balanced versus with no-balanced fluids: in-hospital mortality, acute renal failure with and without dialysis, and hospital and ICU lengths of stay. We also estimated the dose-response relationship between receipt of increasing proportions of balanced fluids and in-hospital mortality. Setting:Three hundred sixty U.S. hospitals that were members of the Premier Healthcare alliance between November 2005 and December 2010. Patients:A total of 53,448 patients with sepsis, treated with vasopressors and crystalloids in an ICU by hospital day 2 including 3,396 (6.4%) that received balanced fluids. Interventions:None. Measurements and Main Results:Patients treated with balanced fluids were younger and less likely to have heart or chronic renal failure, but they were more likely to receive mechanical ventilation, invasive monitoring, colloids, steroids, and larger crystalloid volumes (median 7 vs 5 L). Among 6,730 patients in a propensity-matched cohort, receipt of balanced fluids was associated with lower in-hospital mortality (19.6% vs 22.8%; relative risk, 0.86; 95% CI, 0.78, 0.94). Mortality was progressively lower among patients receiving larger proportions of balanced fluids. There were no significant differences in the prevalence of acute renal failure (with and without dialysis) or in-hospital and ICU lengths of stay. Conclusions:Among critically ill adults with sepsis, resuscitation with balanced fluids was associated with a lower risk of in-hospital mortality. If confirmed in randomized trials, this finding could have significant public health implications, as crystalloid resuscitation is nearly universal in sepsis.

Meta-analysis of high- versus low-chloride content in perioperative and critical care fluid resuscitation

The objective of this systematic review and meta‐analysis was to assess the relationship between the chloride content of intravenous resuscitation fluids and patient outcomes in the perioperative or intensive care setting.

The effect of cyclooxygenase-2 inhibition on acute and chronic donor-site pain after spinal-fusion surgery.

BACKGROUND AND OBJECTIVES The development of chronic pain after spinal-fusion surgery represents a significant source of morbidity. One of the predictive factors for the development of chronic postsurgical pain is inadequate acute postoperative pain management. Further, the up-regulation of cyclooxygenase-2 (COX-2) after surgery may result in neuro-plastic changes that may contribute to a progression from acute to chronic pain. The goal of this prospective, randomized, double-blind study was to examine the effect of perioperative COX-2 inhibition on acute and chronic donor-site pain in patients undergoing spinal-fusion surgery. METHODS Eighty patients scheduled to undergo instrumented posterior spinal fusion were randomized to either receive celecoxib 400 mg 1 hour before surgery, and then 200 mg every 12 hours after surgery for the first 5 days or receive matching placebo at similar time intervals. Patients were administered morphine via patient-controlled analgesia pump for the first 24 hours, and then acetaminophen and oxycodone tablets. Patients were asked to quantify their average pain on postoperative days 1 to 5. At 1 year after surgery, patients were questioned about the presence and subjective characteristics of any residual donor-site pain. RESULTS Patients administered celecoxib reported lower pain scores and less opioid use during the first 5 postoperative days. Chronic donor-site pain was significantly higher (P<.01) in the placebo group (12 of 40, or 30%) compared with the celecoxib group (4 of 40, or 10%) at 1 year after surgery. CONCLUSIONS The administration of celecoxib for the first 5 days after spinal-fusion surgery resulted in improved analgesia and a reduction in chronic donor-site pain at 1 year after surgery.

Fluids are drugs: type, dose and toxicity.

Purpose of reviewWe discuss the formulation of a prescription for intravenous (i.v.) fluid therapy (a ‘volume prescription’) for critically ill patients: pros/cons of different fluid types; accurate dosing; and qualitative and quantitative toxicities. Updated physiologic concepts are invoked and results of recent major clinical trials on i.v. fluid therapy in the acutely ill are interpreted. Recent findingsContext is vital and any fluid can be harmful if dosed incorrectly. When contrasting ‘crystalloid versus colloid’, differences in efficacy are modest, but differences in safety are significant. Differences in chloride load and strong ion difference appear to be clinically important. Quantitative toxicity is mitigated when dosing is based on dynamic parameters that predict volume responsiveness. Qualitative toxicity for colloids (even with newer hydroxyethyl starch 130/0.4 solutions) and isotonic saline remain a concern. SummarySimilar to any drug used in acutely ill patients, clinicians ordering a volume prescription must recognize that context is crucial. Physiologically balanced crystalloids may be the ‘default’ fluid for acutely ill patients, and the role for colloids is unclear. Optimal dosing involves assessment of volume responsiveness.

Association between Initial Fluid Choice and Subsequent In-hospital Mortality during the Resuscitation of Adults with Septic Shock

Background:Currently, guidelines recommend initial resuscitation with intravenous (IV) crystalloids during severe sepsis/septic shock. Albumin is suggested as an alternative. However, fluid mixtures are often used in practice, and it is unclear whether the specific mixture of IV fluids used impacts outcomes. The objective of this study is to test the hypothesis that the specific mixture of IV fluids used during initial resuscitation, in severe sepsis, is associated with important in-hospital outcomes. Methods:Retrospective cohort study includes patients with severe sepsis who were resuscitated with at least 2 l of crystalloids and vasopressors by hospital day 2, patients who had not undergone any major surgical procedures, and patients who had a hospital length of stay (LOS) of at least 2 days. Inverse probability weighting, propensity score matching, and hierarchical regression methods were used for risk adjustment. Patients were grouped into four exposure categories: recipients of isotonic saline alone (“Sal” exclusively), saline in combination with balanced crystalloids (“Sal + Bal”), saline in combination with colloids (“Sal + Col”), or saline in combination with balanced crystalloids and colloids (“Sal + Bal + Col”). In-hospital mortality was the primary outcome, and hospital LOS and costs per day (among survivors) were secondary outcomes. Results:In risk-adjusted Inverse Probability Weighting analyses including 60,734 adults admitted to 360 intensive care units across the United States between January 2006 and December 2010, in-hospital mortality was intermediate in the Sal group (20.2%), lower in the Sal + Bal group (17.7%, P < 0.001), higher in the Sal + Col group (24.2%, P < 0.001), and similar in the Sal + Bal + Col group (19.2%, P = 0.401). In pairwise propensity score–matched comparisons, the administration of balanced crystalloids by hospital day 2 was consistently associated with lower mortality, whether colloids were used (relative risk, 0.84; 95% CI, 0.76 to 0.92) or not (relative risk, 0.79; 95% CI, 0.70 to 0.89). The association between colloid use and in-hospital mortality was inconsistent, and survival was not uniformly affected, whereas LOS and costs per day were uniformly increased. Results were robust in sensitivity analyses. Conclusions:During the initial resuscitation of adults with severe sepsis/septic shock, the types of IV fluids used may impact in-hospital mortality. When compared with the administration of isotonic saline exclusively during resuscitation, the coadministration of balanced crystalloids is associated with lower in-hospital mortality and no difference in LOS or costs per day. When colloids are coadministered, LOS and costs per day are increased without improved survival. A large randomized controlled trial evaluating crystalloid choice is warranted. Meanwhile, the use of balanced crystalloids seems reasonable. (Anesthesiology 2015; 123:1385-93)

Determining the accuracy of caudal needle placement in children: a comparison of the swoosh test and ultrasonography

Background:  The aim of the present study was to compare two confirmatory tests ‐ the ‘swoosh’ test (auscultation during caudal injection) and real time ultrasound imaging (both transverse 2D imaging and color flow Doppler imaging) in pediatric patients receiving a caudal epidural block.

Treatment with neuromuscular blocking agents and the risk of in-hospital mortality among mechanically ventilated patients with severe sepsis

Objectives:Recent trials suggest that treatment with neuromuscular blocking agents may improve survival in patients requiring mechanical ventilation for acute respiratory distress syndrome. We examined the association between receipt of a neuromuscular blocking agent and in-hospital mortality among mechanically ventilated patients with severe sepsis. Design:A pharmacoepidemiologic cohort study of patients with sepsis and a respiratory infection who had been admitted to intensive care and placed on mechanical ventilation within the first 2 days of hospitalization. We used propensity score matching and instrumental variable methods to compare the outcomes of patients treated with neuromuscular blocking agents within the first 2 hospital days to those who were not. Sensitivity analysis was used to model the effects of a hypothetical unmeasured confounder. Setting:Three hundred thirty-nine U.S. hospitals that participated in the Premier Perspective database between 2004 and 2006. Patients:Seven thousand eight hundred sixty-four patients met inclusion criteria, including 1,818 (23%) who were treated with a neuromuscular blocking agent by hospital day 2. Interventions:None. Measurements and Main Results:Patients who received neuromuscular blocking agents were younger (mean age, 62 vs 68), more likely to be treated with vasopressors (69% vs 65%) and had a lower in-hospital mortality rate (31.9% vs 38.3%, p < 0.001). In 3,518 patients matched on the propensity for treatment, receipt of a neuromuscular blocking agent was associated with a reduced risk of in-hospital mortality (risk ratio, 0.88; 95% CI, 0.80, 0.96). An analysis using the hospital neuromuscular blocking agent-prescribing rate as an instrumental variable found receipt of a neuromuscular blocking agent associated with a 4.3% (95% CI, –11.5%, 1.5%) reduction in in-hospital mortality. Conclusions:Among mechanically ventilated patients with severe sepsis and respiratory infection, early treatment with a neuromuscular blocking agent is associated with lower in-hospital mortality.

American Society for Enhanced Recovery (ASER) and Perioperative Quality Initiative (POQI) joint consensus statement on perioperative fluid management within an enhanced recovery pathway for colorectal surgery

BackgroundEnhanced recovery may be viewed as a comprehensive approach to improving meaningful outcomes in patients undergoing major surgery. Evidence to support enhanced recovery pathways (ERPs) is strong in patients undergoing colorectal surgery. There is some controversy about the adoption of specific elements in enhanced recovery “bundles” because the relative importance of different components of ERPs is hard to discern (a consequence of multiple simultaneous changes in clinical practice when ERPs are initiated). There is evidence that specific approaches to fluid management are better than alternatives in patients undergoing colorectal surgery; however, several specific questions remain.MethodsIn the “Perioperative Quality Initiative (POQI) Fluids” workgroup, we developed a framework broadly applicable to the perioperative management of intravenous fluid therapy in patients undergoing elective colorectal surgery within an ERP.DiscussionWe discussed aspects of ERPs that impact fluid management and made recommendations or suggestions on topics such as bowel preparation; preoperative oral hydration; intraoperative fluid therapy with and without devices for goal-directed fluid therapy; and type of fluid.

Ultrasonography and Pediatric Caudals

Ultrasound is an important tool for performing pediatric regional blocks, including caudal blocks. We present a case in which the availability of ultrasound allowed us to proceed with a successful caudal block which we otherwise might have abandoned in an infant with difficult anatomy.

State-of-the-art fluid management in the operating room

The underlying principles guiding fluid management in any setting are very simple: maintain central euvolemia, and avoid salt and water excess. However, these principles are frequently easier to state than to achieve. Evidence from recent literature suggests that avoidance of fluid excess is important, with excessive crystalloid use leading to perioperative weight gain and an increase in complications. A zero-balance approach aimed at avoiding fluid excess is recommended for all patients. For major surgery, there is a sizeable body of evidence that an individualized goal-directed fluid therapy (GDFT) improves outcomes. However, within an Enhanced Recovery program only a few studies have been published, yet so far GDFT has not achieved the same benefit. Balanced crystalloids are recommended for most patients. The use of colloids remains controversial; however, current evidence suggests they can be beneficial in intraoperative patients with objective evidence of hypovolemia.