Prospective Randomized Controlled Trial of Liberal Vs Restricted Perioperative Fluid Management in Patients Undergoing Pancreatectomy.

OBJECTIVE: The aim of this study is to examine, by a prospective randomized controlled trial, the influence of liberal (LIB) vs restricted (RES) perioperative fluid administration on morbidity following pancreatectomy. SUMMARY OF BACKGROUND DATA: Randomized controlled trials in patients undergoing major intra-abdominal surgery have challenged the historical use of LIB fluid administration, suggesting that a more restricted regimen may be associated with fewer postoperative complications. METHODS: Patients scheduled to undergo pancreatic resection were consented for randomization to a LIB (n = 164) or RES (n = 166) perioperative fluid regimen. Sample size was designed with 80% power to decrease Grade 3 complications from 35% to 21%. RESULTS: Between July 2009 and July 2015, we randomized 330 patients undergoing pancreaticoduodenectomy (PD, n = 218), central (n = 16), or distal pancreatectomy (DP, n = 96). Patients were equally distributed for all demographic and intraoperative characteristics. Intraoperatively, LIB patients received crystalloid 12 mL/kg/h and RES patients 6 mL/kg/h. Cumulative crystalloid given (median, range, mL) days 0 to 3 was LIB: 12,252 (6600 to 21,365), RES 7808 (2700 to 16,274) P < 0.0001. Sixty-day mortality was 2 of 330 (0.6%). Median operative time for PD was 227 minutes (105 to 462) and DP 150 (44 to 323). Grade 3 complications occurred in 20% of LIB and 27% of RES patients (P = 0.6). Median length of stay was 7 and 5 days for PD and DP, respectively, in both arms. CONCLUSIONS: In a high volume institution, major perioperative complications from pancreatic resection were not significantly influenced by fluid regimens that differed approximately 1.6-fold.

Mechanical experiments as moral exercise in the education of George III.

In 1761, George III commissioned a large group of philosophical instruments from the London instrument-maker George Adams. The purchase sprang from a complex plan of moral education devised for Prince George in the late 1750s by the third Earl of Bute. Bute's plan applied the philosophy of Frances Hutcheson, who placed 'the culture of the heart' at the foundation of moral education. To complement this affective development, Bute also acted on seventeenth-century arguments for the value of experimental philosophy and geometry as exercises that habituated the student to recognizing truth, and to pursuing it through long and difficult chains of reasoning. The instruments required for such exercise thus became tools for manipulating moral subjectivity. By the 1730s there was a variety of established modes in which the Newtonian philosophy might be used to argue for the legitimacy of Hanoverian rule. The education of George III represents a less recognized iteration of this relationship, concerned not with public apologetics, but rather with the transformation of an 'indolent' youth into a virtuous monarch.

Intraoperative fluid management and complications following pancreatectomy.

BACKGROUND: Considerable debate exists as to appropriate perioperative fluid management. Data from several studies suggest that the amount of fluid administered perioperatively influences surgical outcome. Pancreatic resection is a major procedure in which complications are common. We examined 1,030 sequential patients who had undergone pancreatic resection at Memorial Sloan-Kettering Cancer Center. We documented the prevalence and nature of their complications, and then correlated complications to intraoperative fluid administration. METHODS: We retrospectively examined 1,030 pancreatic resections performed at Memorial Sloan-Kettering Cancer Center between May 2004 and December 2009 from our pancreatic database. Intraoperative administration of colloid and crystalloid was obtained from anesthesia records, and complication data from our institutional database. RESULTS: The overall in-hospital mortality was 1.7%. Operative mortality was due predominantly to intraabdominal infection. Sixty percent of the mortality resulted from intraabdominal complications related to the procedure. We did not demonstrate a clinically significant relationship between intraoperative fluid administration and complications, although minor statistical significance was suggested. CONCLUSIONS: In this retrospective review of intraoperative fluid administration we were not able to demonstrate a clinically significant association between postoperative complications and intraoperative crystalloid and colloid fluid administration. A randomized controlled trial has been initiated to address this question.

ROUTINE USE OF SUGAMMADEX DOES NOT SHORTEN PACU LENGTH OF STAY: A PROSPECTIVE DOUBLE-BLINDED RANDOMIZED CONTROLLED TRIAL.

BACKGROUND: The reversal agent sugammadex has been shown to be more efficacious at reversal from neuromuscular blockade (NMB) induced by the aminosteroid class of non-depolarizing muscle relaxants than the traditionally used medication neostigmine. However, whether these differences lead to significantly faster PACU discharge readiness remains unknown. Given the increased acquisition cost of sugammadex as compared to neostigmine we compared these two reversal agents in our surgical population to determine if its pharmacokinetic superiority warranted a change in current practice. METHODS: We conducted a single-center randomized patient and assessor blinded clinical trial. A total of 201 patients presenting for surgery requiring NMB with an estimated duration of ≤ 6 hours were included in the intention-to-treat (ITT) analysis. The primary outcome was time from reversal agent administration to PACU discharge readiness, measured by either the institutional discharge scoring tool or bedside clinical assessment by a PACU physician or advanced practice provider. Secondary outcomes included subjective assessment of recovery by the patient (pain, visual changes, speaking difficulty, swallowing difficulty, PONV, anxiety) and a simple strength assessment. RESULTS: Median time from reversal administration to PACU discharge readiness was 3.59 hours (IQR 2.49-5.09) in the neostigmine group and 3.62 hours (IQR 2.70-5.87) in the sugammadex group. Patients who received sugammadex had 8% longer reversal to PACU discharge times (exp(estimate) 1.08, 95% CI [0.87-1.34], p=0.499). Patients age 70 or older had 28% longer reversal to PACU discharge times (exp(estimate) of 1.28, 95% CI [0.91-1.80], P=0.158). In the a modified ITT analysis, sugammadex patients were estimated to be in PACU 13% longer than neostigmine arm patients (exp(estimate) 1.13, 95% CI [0.91-1.40], p=0.265) and patients older than or equal to 70 years 31% longer than patients less than 70 years old (exp(estimate) 1.31, 95% CI [0.93-1.84], p=0.121). Treatment arm was not associated with any of the secondary outcomes. CONCLUSION: There was no significant difference in time to readiness to discharge from PACU, and there were no subjective or objective clinically relevant differences in recovery from neuromuscular blockade between the groups. Findings of this study support continued use of either agent at the anesthesiologist's discretion.

Relationship between intraoperative fluid administration and perioperative outcome after pancreaticoduodenectomy: results of a prospective randomized trial of acute normovolemic hemodilution compared with standard intraoperative management.

BACKGROUND: Pancreaticoduodenectomy (PD) can be associated with significant blood loss and transfusion requirements, with potential adverse short- and long-term consequences. The aim of this study was to determine whether acute normovolemic hemodilution (ANH), an established blood conservation technique, reduces perioperative allogeneic transfusions in patients undergoing PD. METHODS: One hundred thirty patients undergoing PD were randomized to ANH or standard management (STDM). In the ANH group, intraoperative blood collection was performed to a target hemoglobin of 8.0 g/dL; crystalloid and colloid were used for volume replacement. Strict transfusion triggers were applied during and after operation. Perioperative complications were prospectively assessed and graded for severity. RESULTS: From July 2005 to May 2009, 209 patients were registered, 79 excluded, 65 were randomized to ANH, and 65 to STD. The groups were well matched for demographic, operative, and histopathologic variables. Patients undergoing ANH received over 2 L more fluid intraoperatively (6250 mL, range 2000-11850) compared with patients undergoing STD (3900 mL, range 2000-9000) (P < 0.001). Transfusion rates were similar (ANH = 16.9%, 30 units vs STD = 18.5%, 33 units; P = 0.82), as was overall perioperative morbidity (ANH = 49.2% vs STD = 47%, P = 0.86). There was, however, a trend toward more grade-3 complications in patients undergoing ANH (32% vs 23.1% STD, P = 0.17), and complications related to the pancreatic anastomosis (leak/fistula/abscess) were significantly higher in the ANH group (21.5% vs 7.7%, P = 0.045). The intraoperative fluid volume was higher for all patients with pancreatic anastomotic complications (n = 19), regardless of randomization arm (ANH 6000 mL, range 2800-11350 mL vs STD 5000 mL, range 2000-11850 mL, P < 0.042). CONCLUSION: In this randomized trial of patients undergoing PD, ANH did not reduce allogeneic transfusions and resulted in more pancreatic anastomotic complications, likely related to greater intraoperative fluid administration. The benefits of ANH do not necessarily extend to all procedures, and restrictive intravenous fluid management during PD may help improve postoperative outcome.

A prospective randomized trial of acute normovolemic hemodilution compared to standard intraoperative management in patients undergoing major hepatic resection.

BACKGROUND: Hepatic resection is the most effective treatment for many malignant and benign conditions affecting the liver and biliary tree. Despite improvements, major partial hepatectomy can be associated with considerable blood loss and transfusion requirements. Transfusion of allogeneic blood products, although potentially life-saving, is associated with many potential complications. The primary aim of this study was to determine if acute normovolemic hemodilution (ANH), an established blood conservation technique, reduces the requirement for allogeneic red cell transfusions in patients undergoing major hepatic resection. METHODS: One hundred thirty patients undergoing major hepatic resection (> or =3 segments) were prospectively randomized to undergo either ANH or standard anesthetic management (STD). In the ANH group, intraoperative blood collection was performed to a target hemoglobin of 8.0 g/dL. Low central venous pressure anesthetic technique was used intraoperatively for both groups. A standardized transfusion protocol was applied to all patients intraoperatively and throughout the hospital stay. RESULTS: From April 2004 to March 2007, 63 patients were randomized to ANH and 67 to STD. Demographics, diagnoses, liver function, extent of resection, intraoperative blood loss, operative time, incidence and grade of complications, and length of hospital stay were similar between the 2 groups. ANH reduced the overall allogeneic red cell transfusion rate by 50% compared with STD [12.7% (n = 8) vs. 25.4% (n = 17), respectively; P = 0.067. ANH patients were less often transfused intraoperatively (n = 1, 1.6%) compared with the STD group (n = 7, 10.4%) (P = 0.036), had higher postoperative hemoglobin levels (P = 0.01), and tended to require fewer red cell units overall (28 vs. 47 units). In patients with intraoperative blood loss > or =800 mL, ANH reduced not only the allogeneic red cell transfusion rate (18.2% vs. 42.4%, P = 0.045) but also the proportion of patients requiring fresh frozen plasma (21.1% vs. 48.3%, P = 0.025). CONCLUSION: For patients undergoing major liver resection, ANH is safe, effectively reduces the need for allogeneic transfusions, and should be considered for routine use. Given the modest transfusion rate in the STD arm, future efforts should attempt to target ANH use to patients most likely to benefit.

Goal-Directed Fluid Therapy Using Stroke Volume Variation for Resuscitation after Low Central Venous Pressure-Assisted Liver Resection: A Randomized Clinical Trial.

BACKGROUND: The optimal perioperative fluid resuscitation strategy for liver resections remains undefined. Goal-directed therapy (GDT) embodies a number of physiologic strategies to achieve an ideal fluid balance and avoid the consequences of over- or under-resuscitation. STUDY DESIGN: In a prospective randomized trial, patients undergoing liver resection were randomized to GDT using stroke volume variation as an end point or to standard perioperative resuscitation. Primary outcomes measure was 30-day morbidity. RESULTS: Between 2012 and 2014, one hundred and thirty-five patients were randomized (GDT: n = 69; standard perioperative resuscitation: n = 66). Median age was 57 years and 56% were male. Metastatic disease comprised 81% of patients. Overall (35% GDT vs 36% standard perioperative resuscitation; p = 0.86) and grade 3 morbidity (28% GDT vs 18% standard perioperative resuscitation; p = 0.22) were equivalent. Patients in the GDT arm received less intraoperative fluid (mean 2.0 L GDT vs 2.9 L standard perioperative resuscitation; p < 0.001). Perioperative transfusions were required in 4% (6% GDT vs 2% standard perioperative resuscitation; p = 0.37) and boluses in the postanesthesia care unit were administered to 24% (29% GDT vs 20% standard perioperative resuscitation; p = 0.23). Mortality rate was 1% (2 of 135 patients; both in GDT). On multivariable analysis, male sex, age, combined procedures, higher intraoperative fluid volume, and fluid boluses in the postanesthesia care unit were associated with higher 30-day morbidity. CONCLUSIONS: Stroke volume variation-guided GDT is safe in patients undergoing liver resection and led to less intraoperative fluid. Although the incidence of postoperative complications was similar in both arms, lower intraoperative resuscitation volume was independently associated with decreased postoperative morbidity in the entire cohort. Future studies should target extensive resections and identify patients receiving large resuscitation volumes, as this population is more likely to benefit from this technique.

Selecting patients for acute normovolemic hemodilution during hepatic resection: a prospective randomized evaluation of nomogram-based allocation.

BACKGROUND: Acute normovolemic hemodilution (ANH) decreases transfusion rates but adds to the complexity of anesthetic management during hepatectomy. A randomized controlled trial was conducted to determine if selecting patients for ANH using a transfusion nomogram improves management and resource use compared with selection using extent of resection. STUDY DESIGN: One hundred fourteen patients undergoing partial hepatectomy were randomized to a clinical arm (ANH used for resection of ≥ 3 liver segments) or a nomogram arm (ANH used for predicted probability of transfusion ≥ 50% based on a previously validated nomogram). The primary end point was appropriate management, defined as avoidance of ANH in patients at low risk or use of ANH in patients at high risk for allogeneic red blood cell transfusions. RESULTS: Between September 2009 and May 2011, 58 patients were randomized to the clinical arm and 56 to the nomogram arm. Demographics, diagnoses, extent of resection, blood loss, and incidence and grade of complications did not differ between the 2 groups. There were no differences in perioperative transfusions or laboratory values. Nomogram-based allocation did not change appropriate management overall (80% vs 76% in the clinical arm; p = 0.65), but did result in comparable perioperative outcomes and a trend toward decreased ANH use (30% vs 47%; p = 0.09), particularly in low blood loss (estimated blood loss ≤ 400 mL) cases (12% vs 25%; p = 0.04). CONCLUSIONS: Although allocation of intraoperative management using a transfusion nomogram did not improve appropriate management overall, it more effectively identified low blood loss cases and reduced ANH use in patients least likely to benefit.

Pancreas and liver resection in Jehovah's Witness patients: feasible and safe.

BACKGROUND: Jehovah's Witness (JW) patients undergoing liver or pancreas surgery represent a challenging ethical and medical problem, with few reports about their optimal management. STUDY DESIGN: To analyze the perioperative outcomes of JW patients submitted to hepatic or pancreatic resection, clinicopathologic data of JW patients who underwent surgical exploration for a hepatic or pancreatic tumor between March 1996 and July 2011 were reviewed retrospectively. RESULTS: Clinicopathologic data of 27 patients, 28 explorations, and 25 resections were included. Median age was 58 years (range 28 to 75 years) and 20 patients were female. Three patients were explored and deemed unresectable. Fifteen hepatic resections (9 segmentectomy or bi/trisegmentectomy, 6 hemi-hepatectomy or extended hepatectomy) and 10 pancreatic resections (6 pancreaticoduodenectomy, 4 distal pancreatectomy/splenectomy) were reviewed; additional organs were resected in 5 patients (2 gastrectomy, 1 colectomy, 1 nephrectomy, 1 adrenalectomy, 1 salpingoophorectomy). Median estimated blood loss for the hepatectomies was 400 mL (range 100 to 1,500 mL) and for the pancreatectomies was 400 mL (range 250 to 1,800 mL). Six patients received preoperative erythropoietin; hemodilution was used in 9 patients and 3 had Cell Saver-generated autotransfusions. Median preoperative hemoglobin was 12.5 g/dL (range 9.5 to 14.4 g/dL) and median postoperative hemoglobin was 10.4 g/dL (range 9 to 12.4 g/dL). In-hospital mortality was 0%. One patient required re-exploration for decreasing hemoglobin and refusal of transfusion; a total of 11 complications developed in 7 other patients (5 wound infection/breakdown, 1 urinary tract infection, 1 ileus, 1 nausea/vomiting, 1 lymphedema, 1 ascites, and 1 ARDS). Median hospital stay was 7 days (range 4 to 23 days). CONCLUSIONS: Pancreatic and liver resection can be done safely in selected JW patients who refuse blood products by using a variety of blood-conservation techniques to help spare red cell mass.

Anesthetic considerations in the multiple endocrine neoplasia syndromes.

PURPOSE OF REVIEW: The multiple endocrine neoplasia (MEN) syndromes present a diverse array of challenges to the anesthesiologist. The tumors and their effects are often underdiagnosed and potentially discovered only when the patient is undergoing surgery for either a component of one of the syndromes or another procedure altogether. This can present the anesthesiologist with a life-threatening situation in the operating room. A thorough understanding of the syndromes, as well as management strategies, will enable the anesthesiologist to handle these patients. RECENT FINDINGS: Advances in the pharmacologic armamentarium available to physicians have enabled patients with MEN, particularly those with the carcinoid syndrome or pheochromocytoma, to undergo surgery safely, with minimal morbidity and mortality. SUMMARY: Awareness of the components of the MEN syndromes, as well as careful preoperative preparation, paves the way for a smooth anesthetic and postoperative course in these patients.

Antifibrinolytic therapy and perioperative blood loss in cancer patients undergoing major orthopedic surgery.

BACKGROUND: Aprotinin has been reported to reduce blood loss and transfusion requirements in patients having major orthopedic operations. Data on whether epsilon amino-caproic acid (EACA) is effective in this population are sparse. METHODS: Sixty-nine adults with malignancy scheduled for either pelvic, extremity or spine surgery during general anesthesia entered this randomized, double-blind, placebo-controlled trial, and received either intravenous aprotinin (n = 23), bolus of 2 x 10(6) kallikrein inactivator units (KIU), followed by an infusion of 5 x 10(5) KIU/h, or EACA (n = 22), bolus of 150 mg/kg, followed by a 15 mg/kg/h infusion or saline placebo (n = 24) during surgery. Our goal was to determine whether prophylactic EACA or aprotinin therapy would reduce perioperative blood loss (intraoperative + first 48h) >30% when compared to placebo. RESULTS: The mean age of the study population was 52 +/- 17 yr. The groups did not differ in age, duration of surgery, perioperative blood loss or number of packed erythrocyte units transfused. When compared to the placebo group, the two treated groups had a significantly lower D-Dimer level immediately after surgery, P < 0.01. CONCLUSIONS: Under the conditions of this study, we were unable to find a clinical benefit to using aprotinin or EACA to reduce perioperative blood loss or transfusion requirements during major orthopedic surgery in cancer patients.