Robert N. Sladen

Association between Increases in Urinary Neutrophil Gelatinase–associated Lipocalin and Acute Renal Dysfunction after Adult Cardiac Surgery

Background:Acute renal dysfunction (ARD) and subsequent acute renal failure after cardiac surgery are associated with high mortality and morbidity. Early therapeutic or preventive intervention is hampered by the lack of an early biomarker for acute renal injury. Recent studies showed that urinary neutrophil gelatinase–associated lipocalin (NGAL or lipocalin 2) is up-regulated early (within 1–3 h) after murine renal injury and in pediatric ARD after cardiac surgery. The authors hypothesized that postoperative urinary NGAL concentrations are increased in adult patients developing ARD after cardiac surgery compared with patients without ARD. Methods:After institutional review board approval, 81 cardiac surgical patients were prospectively studied. Urine samples were collected immediately before incision and at various time intervals after surgery for NGAL analysis by quantitative immunoblotting. ARD was defined as peak postoperative serum creatinine increase by 50% or greater compared with preoperative serum creatinine. Results:Sixteen of 81 patients (20%) developed postoperative ARD, and the mean urinary NGAL concentrations in patients who developed ARD were significantly higher early after surgery (after 1 h: 4,195 ± 6,520 [mean ± SD] vs. 1,068 ± 2,129 ng/ml; P < 0.01) compared with patients who did not develop ARD. Mean urinary NGAL concentrations continued to increase and remained significantly higher at 3 and 18 h after cardiac surgery in patients with ARD. In contrast, urinary NGAL in patients without ARD decreased rapidly after cardiac surgery. Conclusions:Patients developing postoperative ARD had significantly higher urinary NGAL concentrations early after cardiac surgery. Urinary NGAL may therefore be a useful early biomarker of ARD after cardiac surgery. These findings may facilitate the early detection of acute renal injury and potentially prevent progression to acute renal failure.

Use of patient-controlled analgesia to compare the efficacy of epidural to intravenous fentanyl administration.

Fentanyl, unlike morphine, is highly lipophilic and rapidly diffuses out of the epidural space. Respiratory depression is, therefore, unlikely when fentanyl is given epidurally. However, much of fentanyls analgesic effect is mediated by systemic rather than spinal receptor binding. To test this hypothesis, we performed a prospective, double-blind, cross-over study comparing epidural and intravenous (IV) administration of fentanyl in 16 patients for the first 12 h after lower abdominal or lower extremity surgery. To allow direct comparison of these two routes of administration, patient-controlled analgesia was used so patients could self-titrate their analgesia. Patients were randomized to receive fentanyl initially by an epidural (group A, n = 8) or IV (group B, n = 8) catheter for 6 h, after which they were crossed-over to the alternate route by means of a hidden three-way stopcock. The degree of analgesia was subjectively evaluated by a visual analogue scale, and by an observer rating patients comfort and sedation. Cumulative dosage of fentanyl was recorded, and plasma fentanyl concentrations were measured. The onset of analgesia and increase in plasma fentanyl concentrations were more rapid with intravenous fentanyl. However, after 60 min, analgesia (visual analogue scale 2-4 cm) or plasma fentanyl concentrations (0.3-0.7 ng/mL) did not differ between the two routes of administration. There were also no significant differences in the cumulative dosage of fentanyl within each group (epidural vs IV) or between the groups. Thus, the analgesic effects of epidural fentanyl appear largely mediated by systemic absorption. Intravenous fentanyl achieves a similar degree of analgesia and a more rapid onset of effect without the need for epidural catheterization.

Tramadol added to mepivacaine prolongs the duration of an axillary brachial plexus blockade.

UNLABELLED Tramadol is an analgesic drug that is antagonized by alpha2-adrenoceptor antagonists, as well as opioid antagonists. We hypothesized that tramadol might produce effects on an axillary brachial plexus blockade similar to those of clonidine. We designed a prospective, controlled, double-blinded study to assess the impact of tramadol added to mepivacaine on the duration of an axillary brachial plexus blockade. After institutional approval and informed consent, 60 patients (ASA physical status I or II) scheduled for forearm and hand surgery after trauma under brachial plexus anesthesia were included in the study. Patients were randomly assigned to receive either 40 mL of mepivacaine 1% with 2 mL of isotonic sodium chloride solution (Group A, n = 20); 40 mL of mepivacaine 1% with 100 mg of tramadol (Group B, n = 20); or 40 mL of mepivacaine 1% with 2 mL of isotonic sodium chloride solution and 100 mg of tramadol i.v. (Group C, n = 20). Sensory block, motor block, and hemodynamics were recorded before and 5, 10, 30, 60, 120, 180, and 360 min after local anesthetic injection. Duration of sensory and motor block was significantly longer (P < 0.01; P < 0.05) in Group B (299 +/- 84 and 259 +/- 76 min) than in Group A (194 +/- 35 and 181 +/- 24 min) and Group C (187 +/- 35 and 179 +/- 16 min). There was no difference in onset of sensory and motor blockade among groups. Hemodynamics remained unchanged in all patients throughout the study period. We conclude that the addition of tramadol prolongs the duration of brachial plexus block without side effects. Tramadol may be an alternative to epinephrine or clonidine as an adjuvant to local anesthesia for an axillary block. IMPLICATIONS This study demonstrates that the admixture of 100 mg of tramadol with mepivacaine 1% for brachial plexus block provides a pronounced prolongation of blockade without side effects. Our data support a specific analgesic effect of tramadol on peripheral nerves.

Postoperative hypertension : a multicenter, prospective, randomized comparison between intravenous nicardipine and sodium nitroprusside

ObjectiveTo compare the efficacy and safety of iv nicardipine with sodium nitroprusside in the treatment of postoperative hypertension after both cardiac and noncardiac surgery. DesignMulticenter, prospective, randomized, open-label study. SettingSix tertiary referral medical centers (recovery rooms and surgical ICUs). PatientsA total of 139 patients with postoperative hypertension: iv nicardipine (n = 71), sodium nitroprusside (n = 68). InterventionAdministration of iv nicardipine or sodium nitroprusside. MeasurementsVital signs (BP, heart rate), hemodynamic variables, medication dosage, total number of dose changes, and time to achieve BP control were recorded. Main ResultsBoth medications were equally effective in reducing BP in both the cardiac and noncardiac surgical groups. Under the conditions of the study, iv nicardipine controlled hypertension more rapidly than sodium nitroprusside (iv nicardipine 14.0 ± 1.0 mins and sodium nitroprusside 30.4 ± 3.5 mins, p = .0029). The total number of dose changes required to achieve therapeutic BP response was significantly less in the iv nicardipine-treated patients (iv nicardipine 1.5 ± 0.2 vs. sodium nitroprusside 5.1 ± 1.4, p < .05). Adverse effects were observed with both drugs (iv nicardipine 7% [5/71] and sodium nitroprusside 18% [12/68] [NS]). ConclusionsIntravenous nicardipine is as effective as sodium nitroprusside in the therapy of postoperative hypertension. Specific advantages have been identified. The use of iv nicardipine should be considered in the therapy of postoperative hypertension. (Crit Care Med 1992; 20:1637–1643)

Pharmacology of sedative-analgesic agents: dexmedetomidine, remifentanil, ketamine, volatile anesthetics, and the role of peripheral mu antagonists.

In this article, the authors discuss the pharmacology of sedative-analgesic agents like dexmedetomidine, remifentanil, ketamine, and volatile anesthetics. Dexmedetomidine is a highly selective alpha-2 agonist that provides anxiolysis and cooperative sedation without respiratory depression. It has organ protective effects against ischemic and hypoxic injury, including cardioprotection, neuroprotection, and renoprotection. Remifentanil is an ultra-short-acting opioid that acts as a mu-receptor agonist. Ketamine is a nonbarbiturate phencyclidine derivative and provides analgesia and apparent anesthesia with relative hemodynamic stability. Volatile anesthetics such as isoflurane, sevoflurane, and desflurane are in daily use in the operating room in the delivery of general anesthesia. A major advantage of these halogenated ethers is their quick onset, quick offset, and ease of titration in rendering the patient unconscious, immobile, and amnestic.

Guidelines for critical care medicine training and continuing medical education.

ObjectiveCritical care medicine trainees and faculty must acquire and maintain the skills necessary to provide state-of-the art clinical care to critically ill patients, to improve patient outcomes, optimize intensive care unit utilization, and continue to advance the theory and practice of critical care medicine. This should be accomplished in an environment dedicated to compassionate and ethical care. ParticipantsA multidisciplinary panel of professionals with expertise in critical care education and the practice of critical care medicine under the direction of the American College of Critical Care Medicine. ScopePhysician education in critical care medicine in the United States should encompass all disciplines that provide care in the intensive care unit and all levels of training: from medical students through all levels of postgraduate training and continuing medical education for all providers of clinical critical care. The scope of this guideline includes physician education in the United States from residency through ongoing practice after subspecialization. Data Sources and SynthesisRelevant literature was accessed via a systematic Medline search as well as by requesting references from all panel members. Subsequently, the bibliographies of obtained literature were reviewed for additional references. In addition, a search of organization-based published material was conducted via the Internet. This included but was not limited to material published by the American College of Critical Care Medicine, Accreditation Council for Graduate Medical Education, Accreditation Council for Continuing Medical Education, and other primary and specialty organizations. Collaboratively and iteratively, the task force met, by conference call and in person, to construct the tenets and ultimately the substance of this guideline. ConclusionsGuidelines for the continuum of education in critical care medicine from residency through specialty training and ongoing throughout practice will facilitate standardization of physician education in critical care medicine.

Treatment of Acute Postoperative Hypertension in Cardiac Surgery Patients: An Efficacy Study of Clevidipine Assessing Its Postoperative Antihypertensive Effect in Cardiac Surgery-2 (ESCAPE-2), a Randomized, Double-Blind, Placebo-Controlled Trial

BACKGROUND: Acute postoperative hypertension is a well-known complication of cardiac surgery and is associated with postoperative morbidity. Clevidipine, an ultrashort-acting, third-generation dihydropyridine calcium channel blocker, exerts vascular-selective, arterial-specific vasodilation to decrease arterial blood pressure without negatively impacting cardiac function. In this double-blind, placebo-controlled trial, we examined the efficacy and safety of clevidipine in treating postoperative hypertension in cardiac surgery patients. METHODS: Two hundred six patients undergoing cardiac surgery were randomized preoperatively. Of these, 110 met postrandomization inclusion criteria for the study [systolic blood pressure (SBP) ≥140 mm Hg within 4 h of admission to a postoperative setting, and clinically assessed as needing SBP reduction by ≥15% from baseline]. Patients received an infusion of either clevidipine (0.4–8.0 &mgr;g kg−1 min−1) or 20% lipid emulsion (placebo) for 30 min to a maximum of 1 h unless treatment failure occurred sooner. The primary end point was the incidence of treatment failure, defined as the inability to decrease SBP by ≥15% from baseline, or the discontinuation of study treatment for any reason within the 30-min period after study drug initiation. RESULTS: Clevidipine-treated patients had a significantly lower incidence of treatment failure than placebo patients [8.2% (5 of 61) vs 79.6% (39 of 49), P < 0.0001]. Treatment success was achieved in 91.8% of clevidipine-treated patients. Median time to target SBP with clevidipine was 5.3 min (95% confidence interval, 4–7 min). No clinically significant increase in heart rate from baseline was observed. Adverse event rates were similar for both treatment groups. CONCLUSIONS: Clevidipine is effective and safe in the rapid treatment of acute postoperative hypertension after cardiac surgery.

Cost-Benefit and Efficacy of Aprotinin Compared with ε-Aminocaproic Acid in Patients Having Repeated Cardiac Operations A Randomized, Blinded Clinical Trial

Background: Aprotinin and epsilon‐aminocaproic acid are routinely used to reduce bleeding during cardiac surgery. The marked difference in average wholesale cost between these two drug therapies (aprotinin,

Colorimetric end-tidal carbon dioxide monitoring for tracheal intubation

1,080 vs. epsilon‐aminocaproic acid,

Population Pharmacodynamics of Midazolam Administered by Target Controlled Infusion in SICU Patients after CABG Surgery

11) has generated significant controversy regarding their relative efficacies and costs. Methods: In a multicenter, randomized, prospective, blinded trial, patients having repeated cardiac surgery received either a high‐dose regimen of aprotinin (total dose, 6 x 106 kallikrein inactivator units) or epsilon‐aminocaproic acid (total dose, 270 mg/kg). Results: Two hundred four patients were studied. Overall (data are median [25th‐75th percentiles]), aprotinin‐treated patients had less postoperative thoracic drainage (511 ml [383–805 ml] vs. 655 ml [464–1,045 ml]; P = 0.016) and received fewer platelet transfusions (0 [range, 0–1] vs. 1 [range, 0–2]; P = 0.036). The surgical field was more likely to be considered free of bleeding in aprotinin‐treated patients (44% vs. 26%; P = 0.012). No differences, however, were seen in allogeneic erythrocyte transfusions or in the time required for chest closure. Overall, direct and indirect bleeding‐related costs were greater in aprotinin‐ than in epsilon‐aminocaproic acid‐treated patients (