David P. Maguire

The HYSLAR trial: a prospective randomized controlled trial of the use of a restrictive fluid regimen with 3% hypertonic saline versus lactated Ringers in patients undergoing pancreaticoduodenectomy.

Objective:This study was designed to determine whether the volume and type of fluid administered for pancreaticoduodenectomy impacts postoperative outcomes. Background:Three percent hypertonic saline (HYS) has been suggested as a means of reducing the volume of fluid required to sustain tissue perfusion in the perioperative period. Methods:Between May 2011 and November 2013, patients undergoing pancreaticoduodenectomy were enrolled in an institutional review board–approved, single-center, prospective, parallel, randomized controlled trial (NCT 01428050), comparing lactated Ringers (LAR) (15 mL/kg/hr LAR intraoperation, 2 mL/kg/hr LAR postoperation) with HYS (9 mL/kg/hr LAR and 1 mL/kg/hr HYS intraoperation, 1 mL/kg/hr HYS postoperation). Results:A total of 264 patients were randomized. Demographic variables between groups were similar. The HYS patients had a significantly reduced net fluid balance (65 vs 91 mL/kg, P = 0.02). The overall complication rate was reduced in the HYS group (43% vs 54%), with a relative risk of 0.79 [95% confidence interval (CI), 0.62–1.02; P = 0.073], factoring stratification for pancreas texture. After adjustment for age and weight, the relative risk was 0.75 [95% CI (0.58–0.96); P = 0.023]. The total number of complications was significantly reduced in the HYS group (93 vs 123), with an incidence rate ratio of 0.74 [95% CI (0.56–0.97); P = 0.027]. After adjustment for age and weight, the incidence rate ratio was 0.69 [95% CI (0.52–0.90); P = 0.0068]. Reoperations, length of stay, readmissions, and 90-day mortality were similar between groups. Conclusions:A moderately restrictive fluid regimen with HYS resulted in a statistically significant 25% reduction in complications when adjusted for age, weight, and pancreatic texture.

Nicardipine versus placebo for the treatment of postoperative hypertension

Postoperative hypertension can cause serious complications, including bleeding from fresh anastomoses, cardiovascular accident, and myocardial ischemia. Therefore rapid control of blood pressure is essential to prevent poor outcome. In this study, 30 American Society of Anesthesiologists class I and II patients who did not have cardiac surgery and subsequently developed postoperative hypertension were randomly assigned to receive either nicardipine, a new dihydropyridine calcium channel blocker, or placebo. Intravenous nicardipine was given as a loading bolus of 10 mg/hr for 5 minutes and was titrated to 15 mg/hr if needed to achieve a therapeutic response. After therapeutic response, intravenous nicardipine was decreased to 3 mg/hr and subsequently titrated in increments of 1.0 to 2.5 mg/hr to maintain blood pressure control. Systolic and diastolic blood pressures during titration and maintenance did not differ significantly from preoperative levels in patients treated with nicardipine. The mean time to therapeutic response for the nicardipine-treated group was 8.67±1.46 minutes, and the median time to offset of action was 15 minutes. Eleven of the 12 patients who received placebo were crossed over to antihypertensive therapy, and of these, 10 received intravenous nicardipine. In this group all achieved therapeutic response in 7.3±1.18 minutes. The usefulness of intravenous nicardipine for postoperative hypertension was demonstrated in this study by: (1) the rapid control of blood pressure, (2) its continued efficacy during maintenance, and (3) little need to adjust dosage to control blood pressure.

Nephrotoxicity of hexachloro-1:3-butadiene in the male Hanover Wistar rat; correlation of minimal histopathological changes with biomarkers of renal injury†

Hexachloro‐1:3‐butadiene (HCBD) causes damage specifically to the renal proximal tubule in rats. In the present study, injury to the nephron of male Hanover Wistar rats was characterized at 24 h following dosing with HCBD in the range 5–90 mg kg−1 to determine the most sensitive biomarkers of damage, that is, the biomarkers demonstrating significant changes at the lowest dose of HCBD, using a range of measurements in serum and urine, renal histopathology, and renal and hepatic gene expression. Histologically, kidney degeneration was noted at doses as low as 10 mg kg−1 HCBD. Significant changes in the hepatic and renal gene expression categories of xenobiotic metabolism and oxidative stress were observed at 5 mg kg−1 HCBD, and in the kidney alone, evidence of inflammation at 90 mg kg−1 HCBD. Increases in the urinary excretion of α‐glutathione S‐transferase (α‐GST) and kidney injury molecule‐1 (KIM‐1) were seen at 10 mg kg−1 HCBD, and increases in urinary excretion of albumin and total protein were evident at 15 mg kg−1 HCBD. The most sensitive, noninvasive biomarkers of HCBD‐induced renal toxicity in Hanover Wistar rats were urinary α‐GST and KIM‐1. Urinary albumin measurement is also recommended as, although it is not the most sensitive biomarker, together with α‐GST, albumin showed the largest relative increase of all the biomarkers investigated, and the protein is easily measured. Copyright

Anesthetic Implications for Patients with Rate-Responsive Pacemakers:

One hundred thousand adults and children in the United States receive pacemakers each year, of which 85% are rateresponsive pacemakers (RRPs). Recent advances in the fields of computer programming and computer chip technology have led to the myriad development of RRPs, which contain sensors that automatically adjust the pacing rate to match the physiologic changes that occur during physical exertion. Because patients with RRPs may experience heart rate changes in the operating room due to “normal” sensor function, anesthesiologists must be aware of the new developments in RRP sensor technology to properly manage these patients. Increases in respiratory rate and tidal volume as well as the use of electrocautery have been reported to accelerate the paced rate of pacemakers with minute ventilation sensors. Likewise, patient movement and saws that produce vibrations can accelerate the paced rate of patients with piezoelectric crystal sensors. This paper discusses the history of pacemaker development, reviews the currently used RRP sensors, and recommends procedures for the perioperative management of these patients. Knowledge of sensor type and factors that stimulate them will help the anesthesiologist understand the cause of these changes so that he will be able to manage clinically significant hemodynamic changes due to RRP sensor activation.

NICARDIPINE VS. PLACEBO FOR THE TREATMENT OF POSTOPERATIVE HYPERTENSION

Postoperative hypertension can cause serious complications, including bleeding from fresh anastomoses, cardiovascular accident, and myocardial ischemia. Therefore rapid control of blood pressure is essential to prevent poor outcome. In this study, 30 American Society of Anesthesiologists class I and II patients who did not have cardiac surgery and subsequently developed postoperative hypertension were randomly assigned to receive either nicardipine, a new dihydropyridine calcium channel blocker, or placebo. Intravenous nicardipine was given as a loading bolus of 10 mg/hr for 5 minutes and was titrated to 15 mg/hr if needed to achieve a therapeutic response. After therapeutic response, intravenous nicardipine was decreased to 3 mg/hr and subsequently titrated in increments of 1.0 to 2.5 mg/hr to maintain blood pressure control. Systolic and diastolic blood pressures during titration and maintenance did not differ significantly from preoperative levels in patients treated with nicardipine. The mean time to therapeutic response for the nicardipine-treated group was 8.67 +/- 1.46 minutes, and the median time to offset of action was 15 minutes. Eleven of the 12 patients who received placebo were crossed over to antihypertensive therapy, and of these, 10 received intravenous nicardipine. In this group all achieved therapeutic response in 7.3 +/- 1.18 minutes. The usefulness of intravenous nicardipine for postoperative hypertension was demonstrated in this study by: (1) the rapid control of blood pressure, (2) its continued efficacy during maintenance, and (3) little need to adjust dosage to control blood pressure.

Autotriggering during pressure support ventilation due to cardiogenic oscillations.

Newer generation anesthesia machines are equipped with a pressure support mode of ventilation, which can be used to support spontaneous ventilation in anesthetized patients. The Drager Apollo anesthesia machine uses an inspiratory limb hot-wire flow sensor to measure inspiratory flow rates. Detected flow rates that exceed the pressure support flow trigger will trigger pressure support breaths (Internal communication document. Drager Medical, 2007). In the case we are presenting, cardiac oscillations produced inspiratory flow rates that exceeded the flow trigger and autotriggered pressure support breaths. Autotriggering could be suppressed by increasing the trigger threshold or the positive end-expiratory pressure setting.

Correlation of Histopathology, Urinary Biomarkers, and Gene Expression Responses Following Hexachloro-1:3-Butadiene–induced Acute Nephrotoxicity in Male Hanover Wistar Rats: A 28-day Time Course Study

Hexachloro-1:3-butadiene (HCBD) causes segment-specific injury to the proximal renal tubule. A time course study of traditional and more recently proposed urinary biomarkers was performed in male Hanover Wistar rats receiving a single intraperitoneal (ip) injection of 45 mg/kg HCBD. Animals were killed on days 1, 2, 3, 4, 5, 6, 7, 10, 14, and 28 postdosing and the temporal response of renal biomarkers was characterized using kidney histopathology, urinary and serum biochemistry, and gene expression. Histopathologic evidence of tubular degeneration was seen from day 1 until day 3 postdosing and correlated with increased urinary levels of α-glutathione S-transferase (α-GST), albumin, glucose, and kidney injury molecule-1 (KIM-1), and increased gene expression of KIM-1, NAD(P)H dehydrogenase, quinone 1, and heme oxygenase (decycling) 1. Histopathologic evidence of tubular regeneration was seen from day 2 postdosing and correlated with raised levels of urinary KIM-1 and osteopontin and increased gene expression of KIM-1 and annexin A7. Traditional renal biomarkers generally demonstrated low sensitivity. It is concluded that in rat proximal tubular injury, measurement of a range of renal biomarkers, in conjunction with gene expression analysis, provides an understanding of the extent of degenerative changes induced in the kidney and the process of regeneration.

Effect of heparin-bonded pulmonary artery catheters on the activated coagulation time

OBJECTIVE This study evaluated the effect of a heparin-bonded pulmonary artery catheter (PAC) on the activated coagulation time (ACT). DESIGN A prospective, controlled comparison. SETTING A tertiary care university hospital. PARTICIPANTS Adult cardiac surgery patients. INTERVENTIONS Celite ACTs were measured from arterial and central venous blood samples before and after the insertion of a heparin-bonded PAC. Thromboelastograms were also obtained from central venous blood samples before and 2 minutes after PAC insertion. MEASUREMENTS AND MAIN RESULTS There was no significant difference between the sample sites before PAC insertion. After PAC insertion, the central venous ACTs were significantly increased compared with the corresponding arterial measurements at 2, 5, 10, and 20 minutes (p < 0.005, analysis of variance [ANOVA] for repeated measures, Fishers protected least significant difference [PLSD]). The 2-minute post-PAC reaction time from the central venous blood sample was greater than 60 minutes in all cases. CONCLUSION The heparin-bonded PAC was associated with a localized, time-dependent alteration in the ACT. Whenever possible, blood samples for baseline ACT measurements should be obtained from an arterial catheter to minimize the anticoagulant effects from the PAC.

Economic and Environmental Considerations During Low Fresh Gas Flow Volatile Agent Administration After Change to a Nonreactive Carbon Dioxide Absorbent.

BACKGROUND:Reducing fresh gas flow (FGF) during general anesthesia reduces costs by decreasing the consumption of volatile anesthetics and attenuates their contribution to greenhouse gas pollution of the environment. The sevoflurane FGF recommendations in the Food and Drug Administration package insert relate to concern over potential toxicity from accumulation in the breathing circuit of compound A, a by-product of the reaction of the volatile agent with legacy carbon dioxide absorbents containing strong alkali such as sodium or potassium hydroxide. Newer, nonreactive absorbents do not produce compound A, making such restrictions moot. We evaluated 4 hypotheses for sevoflurane comparing intervals before and after converting from a legacy absorbent (soda lime) to a nonreactive absorbent (Litholyme®): (1) intraoperative FGF would be reduced; (2) sevoflurane consumption per minute of volatile agent administration would be reduced; (3) cost savings due to reduced sevoflurane consumption would (modestly) exceed the incremental cost of the premium absorbent; and (4) residual wastage in discarded sevoflurane bottles would be <1%. METHODS:Inspired carbon dioxide (PICO2), expired carbon dioxide, oxygen, air, and nitrous oxide FGF, inspired volatile agent concentrations (FiAgent), and liquid volatile agent consumption were extracted from our anesthesia information management system for 8 4 week intervals before and after the absorbent conversion. Anesthesia providers were notified by e-mail and announcements at Grand Rounds about the impending change and were encouraged to reduce their average intraoperative sevoflurane FGF to 1.25 L/min. Personalized e-mail reports were sent every 4 weeks throughout the study period regarding the average intraoperative FGF (i.e., from surgery begin to surgery end) for each agent. Batch means methods were used to compare FGF, volatile agent consumption, net cost savings, and residual sevoflurane left in bottles to be discarded in the trash after filling vaporizers. The time from reaching a PICO2 = 3 mm Hg for 3 minutes until agent exhaustion (PICO2 = 5 mm Hg for 5 minutes) was evaluated. RESULTS:A total of N = 20,235 cases were analyzed (80.2% sevoflurane, 15.1% desflurane, and 4.7% isoflurane). Intraoperative FGF was reduced for cases in which sevoflurane was administered by 435 mL/min (95% confidence interval [CI], 391 to 479 mL/min; P < 10−5). Hypothesis 1 was accepted. Sevoflurane consumption per minute of administration decreased by 0.039 mL/min (95% CI, 0.029 to 0.049 mL/min; P < 10−5) after the change to the nonreactive absorbent. Hypothesis 2 was accepted. The difference in mean cost for the sum of the sevoflurane and absorbent purchases for each of the 10 4-week intervals before and after the absorbent switch was −

An alternate method for calibrating the thrombelastograph

293 per 4-week interval (95% CI, −