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Biomedical subjects

R N Sladen

Publications and source records attributed to R N Sladen.

At least 19 recordsLinked to original sources

Nitric oxide for the treatment of postpneumonectomy pulmonary edema.

Inhaled nitric oxide, a selective pulmonary vasodilator, has been used to improve arterial oxygenation in adult respiratory distress syndrome. To our knowledge, it has not been successfully used to treat this syndrome after major lung resection. We used nitric oxide to treat postpneumonectomy pulmonary edema with immediate and sustained improvement in oxygenation. The patient was successfully weaned from nitric oxide and extubated after 3 days of supportive therapy.

Administration, Inhalation↗

Renal function and dysfunction.

Recent publications regarding perioperative renal dysfunction provide a 'potpourri' of topics worthy of discussion. The risk of perioperative renal dysfunction is higher in patients with heart failure, but other pre-existing conditions, such as genetic polymorphism, may have prognostic implications. Evaluation of renal risk and protective interventions are discussed for a number of specific operative entities, including cardiac surgery (with or without cardiopulmonary bypass), aortic surgery and renal revascularization. New publications on a wide variety of nephrotoxic insults are presented, including antifibrinolytic agents, obstructive jaundice, prostaglandin inhibitors, cyclosporine A, radiocontrast dyes and volatile anesthetic agents. Renal transplantation is discussed as a specific entity. Finally, we discuss recent papers describing outcome in patients in chronic renal failure undergoing cardiac surgery.

Journal Article↗

Oliguria in the ICU. Systematic approach to diagnosis and treatment.

Perioperative oliguria is common but rarely implies acute renal failure. We should interpret oliguria as a sign of intravascular hypovolemia and treat it as prerenal until proven otherwise. On the other hand, the absence of oliguria does not exclude acute renal failure. The most reliable clinical indicator of progressive renal dysfunction is a serial decline in creatinine clearance estimation, a measure of glomerular filtration rate.

Acute Kidney Injury↗

Renal blood flow regulation, autoregulation, and vasomotor nephropathy.

Renal blood flow and renal perfusion pressure are regulated by two control mechanisms. The first, extrinsic, actually involves a complex interaction of vasomotor effects between opposing neurohormonal systems. The second, intrinsic mechanism, renal autoregulation, depends on changes in afferent arteriolar tone in response to the renal perfusion pressure itself. This article reviews these two mechanisms, how they normally respond to stress, and the clinical implications of certain situations in which these control mechanisms are disrupted.

Cardiopulmonary Bypass↗

Anesthetic considerations for the patient with renal failure.

Patients in end-stage renal disease and chronic liver failure present a number of challenges to the anesthesiologist. They may be chronically ill and debilitated and have the potential for multisystem organ dysfunction. To safely manage these patients we need to understand the benefits and limitations of dialysis and the altered pharmacology of commonly used anesthetic agents and perioperative medications in chronic renal failure.

Anesthesia↗

Tromethamine buffer modifies the depressant effect of permissive hypercapnia on myocardial contractility in patients with acute respiratory distress syndrome.

In patients with acute respiratory distress syndrome (ARDS), permissive hypercapnia is a strategy to decrease airway pressures to prevent ventilator-induced lung damage by lowering tidal volumes and tolerating higher arterial carbon dioxide tension. However, in experimental studies hypercapnia impairs myocardial contractility and hemodynamic function. We investigated the effect of short-term permissive hypercapnia on myocardial contractility and hemodynamics in patients with ARDS. We hypothesized that the administration of tromethamine (THAM), a buffer which does not increase carbon dioxide production, would modify these changes. In 12 patients with ARDS, permissive hypercapnia was implemented for 2 h with a target Pa(CO(2))of 80 mm Hg. Patients were randomized to have respiratory acidosis corrected by THAM (pH-corrected group), or not corrected (pH-uncorrected group). Hemodynamic responses were measured, and transesophageal echocardiography (TEE) was used to determine myocardial contractility. Permissive hypercapnia resulted in significant decreases in systemic vascular resistance (SVR) and increases in cardiac output (Q). Myocardial contractility decreased in both groups but significantly less in the pH-corrected group (approximately 10%) than in the pH-uncorrected group (approximately 18%, p < 0.05). Mean arterial pressure decreased and mean pulmonary arterial pressure increased significantly only in the pH-uncorrected group. All values returned to baseline conditions 1 h after permissive hypercapnia was terminated. Our study demonstrates a reversible depression of myocardial contractility and hemodynamic alterations during rapid permissive hypercapnia which were attenuated by buffering with THAM. This may have applicability to the clinical strategy of permissive hypercapnia and allow the benefit of decreased airway pressures to be realized while minimizing the adverse hemodynamic effects of hypercapnic acidosis.

Acid-Base Equilibrium↗

Lactate in sepsis and trauma--hindrance or help?

Physiologic hyperlactatemia must be distinguished from lactate acidosis (lactate > 5 mM/L, pH < 7.32). Sustained lactic acidosis, or changes in lactate in response to inotropic support, are useful predictors of mortality in severe sepsis and trauma, and superior to hemodynamic markers such as DO2 and VO2. Base deficit is a readily available surrogate for plasma lactate, and the addition of gastric tonometry enhances its predictive ability.

Acidosis, Lactic↗

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.

Adult↗

Controlled airway pressure therapy, nitric oxide inhalation, prone position, and extracorporeal membrane oxygenation (ECMO) as components of an integrated approach to ARDS.

BACKGROUND: Recent years have seen the introduction of innovative additive therapies for acute respiratory distress syndrome. However, because there are no reliable predictors of response to a particular therapy, potential responders to a specific therapeutic intervention may be lost. Therefore, the authors evaluated the effect of a combined therapeutic approach on the survival of patients with acute respiratory distress syndrome, when treated according to a strict algorithm. METHODS: During a 2.5-yr period, 84 patients with acute respiratory distress syndrome were assigned to a standardized treatment protocol. Data analysis was performed by retrospective review of patient charts. Patients were treated using a stepwise treatment algorithm of pressure-controlled ventilation (peak airway pressure < 35 cm H2O), positive end-expiratory pressure (PEEP; 12-15 cm H2O), permissive hypercapnia, inhaled nitric oxide (5-20 ppm), and prone positioning. These interventions were termed "conventional therapy." Response to treatment was defined as a more than 20% increase in arterial oxygen tension (PaO2). Nonresponders were triaged to extracorporeal membrane oxygenation. RESULTS: The overall survival rate was 80%. All patients received conventional therapy up to 96 h; 71 responded to conventional therapy and 59 survived (83%). Thirteen patients (15%) did not respond to conventional therapy and underwent extracorporeal membrane oxygenation; 8 of these patients (62%) survived. For the group, the mean admission lung injury score was 3.3+/-0.5, the PaO2/fractional inspired oxygen tension (F(I)O2) ratio was 96+/-45, and the Acute Physiology and Chronic Health Evaluation (APACHE) II score was 18+/-6. CONCLUSIONS: The 80% overall survival rate achieved in this group of patients with severe acute respiratory distress syndrome may in part reflect the additive beneficial effects of combined treatment methods, such as airway pressure control, nitric oxide inhalation, prone position, and early triage of nonresponders to extracorporeal membrane oxygenation.

APACHE↗

New hemoglobin substitutes.

Blood transfusion is an essential and ubiquitous component of medical therapy. Despite careful screening and processing, allogeneic blood still carries a small but definable risk of the transmission of severe viral disease and the induction of immunological reactions. The logistics of its storage and transport continue to present a challenge, and its dependence on human donors will always keep it a scarce resource. It is not surprising that in the latter half of the 20th century efforts to develop blood substitutes have gained increasing momentum.

Journal Article↗

The arterial to end-tidal carbon dioxide gradient increases with uncorrected but not with temperature-corrected PaCO2 determination during mild to moderate hypothermia.

UNLABELLED: End-tidal carbon dioxide (PETCO2) monitoring is recommended as a basic standard of care and is helpful in adjusting mechanical ventilation. Gas solubility changes with temperature, which might affect the PaCO2 and thereby the gradient between PaCO2 and PETCO2 (PA-ETCO2) under hypothermic conditions. We investigated whether the PA-ETCO2 changes during mild to moderate hypothermia (36 degrees C-32 degrees C) using PaCO2 measured at 37 degrees C (uncorrected PaCO2) and PaCO2 corrected to actual body temperature. We preoperatively investigated 19 patients. After anesthesia had been induced, controlled ventilation was established to maintain normocarbia using constant uncorrected PaCO2 to adjust ventilation (alpha-stat acid-base regimen). Body core temperature was reduced without surgical intervention to 32 degrees C by surface cooling. Continuous PETCO2 was monitored with a mainstream PETCO2 module. The PA-ETCO2 was calculated using the uncorrected and corrected PaCO2 values. During body temperature reduction from 36 degrees C to 32 degrees C, the gradient between PETCO2 and uncorrected PaCO2 increased 2.5-fold, from 4.1 +/- 3.7 to 10.4 +/- 3.8 mm Hg (P < 0.002). The PA-ETCO2 remained unchanged when the corrected PaCO2 was used for the calculation. We conclude that when the alpha-stat acid-base regimen is used to adjust ventilation, the PA-ETCO2 calculated with the uncorrected PaCO2 increases and should be added to the differential diagnosis of widened PA-ETCO2. In contrast, when the corrected PaCO2 is used for the calculation of the PA-ETCO2, the PA-ETCO2 remains unaltered during hypothermia. IMPLICATIONS: We investigated the impact of induced hypothermia (36 degrees C-32 degrees C) on the gradient between PaCO2 and PETCO2 (PA-ETCO2). The PA-ETCO2 increased 2.5-fold when CO2 determinations were not temperature-corrected. Hypothermia should be added to the differential diagnosis of an increased PA-ETCO2 when the alpha-stat acid-base regimen is used.

Adult↗

Catheter-induced thrombus in the superior vena cava diagnosed by transesophageal echocardiography.

BACKGROUND: To present the role of transesophageal echocardiography (TEE) in the diagnosis and management of catheter-related superior vena cava thrombosis. CASE HISTORY: A 42-year-old woman with severe Crohn's disease presented with septic shock and pulmonary embolism three weeks after emergency laparotomy and ileocolic resection for small-bowel perforation with peritonitis. Cardiopulmonary evaluation with ECG, pulmonary artery catheter and TEE demonstrated no evidence of acute myocardial ischemia or ventricular dysfunction; hemodynamic indices were consistent with severe sepsis. TEE revealed a large sheathing thrombus surrounding a central venous catheter used for parenteral nutrition. A spiral CT scan of the chest confirmed multiple peripheral pulmonary emboli. Treatment consisted of systemic anticoagulation and antibiotics. To avoid further pulmonary embolism, the central venous catheter was not removed until six days later under TEE monitoring, which revealed that the thrombus was firmly adherent to the superior vena cava. The patient made an uneventful recovery and was discharged from hospital on long-term anticoagulant therapy. CONCLUSION: In a case of catheter-induced superior vena cava thrombosis with septicemia and pulmonary embolism, bedside TEE was very helpful to make the correct diagnosis early, assess thrombus size during anticoagulation, and monitor cardiac performance and thrombus disposition during central venous catheter removal.

Adult↗

The effects of epsilon-aminocaproic acid on fibrinolysis and thrombin generation during cardiac surgery.

UNLABELLED: Despite the efficacy of antifibrinolytic drugs in reducing bleeding after cardiac surgery, concerns remain regarding their potential to promote thrombosis. We examined the effect of the antifibrinolytic drug, epsilon-aminocaproic acid (EACA) on fibrinolysis and thrombin generation during cardiac surgery. Forty-one adults undergoing primary coronary artery bypass graft surgery requiring cardiopulmonary bypass (CPB) were prospectively randomized in a double-blind trial to receive either saline or EACA. A loading dose of 150 mg/kg EACA was given before anesthetic induction, followed by a 15 mg x kg(-1) x h(-1) infusion, which continued until 3 h after CPB. Plasma samples for the measurement of D-dimer, thrombin-antithrombin III, and soluble fibrin were obtained before surgery, 1 h on CPB, and 3 and 20 h after CPB. In the EACA group, fibrinolytic activity, as measured by D-dimer, was significantly decreased 3 h after CPB, (0.51 +/- 0.15 mg/L vs 1.13 +/- 0.14 mg/L, P < 0.005). Decreased fibrinolytic activity was accompanied by decreased bleeding in the EACA group (660 +/- 127 mL vs 931 +/- 113 mL, P < 0.05). No differences in the generation of thrombin or soluble fibrin were apparent between the two groups. Suppression of fibrinolytic activity in the absence of concomitant reductions in thrombin generation suggests that EACA could potentiate a hypercoagulable prethrombotic state in the perioperative setting. IMPLICATIONS: In a randomized, prospective trial of primary cardiac surgery, we demonstrated that the synthetic antifibrinolytic drug epsilon-aminocaproic acid suppresses fibrinolysis with no effects on thrombin generation. These results suggest the potential for synthetic antifibrinolytic drugs to induce a hypercoagulable prethrombotic state in the perioperative setting.

Aminocaproic Acid↗

Cost-benefit and efficacy of aprotinin compared with epsilon-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, $1,080 vs. epsilon-aminocaproic acid, $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 10(6) 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 ($1,813 [$1,476-2,605] vs. $1,088 [range, $511-2,057]; P = 0.0001). This difference in cost per case varied in magnitude among sites but not in direction. CONCLUSIONS: Aprotinin was more effective than epsilon-aminocaproic acid at decreasing bleeding and platelet transfusions. Epsilon-aminocaproic acid, however, was the more cost-effective therapy over a broad range of estimates for bleeding-related costs in patients undergoing repeated cardiac surgery. A cost-benefit analysis using the lower cost of half-dose aprotinin ($540) still resulted in a significant cost advantage using epsilon-aminocaproic therapy (P = 0.022).

Adult↗