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Biomedical subjects

H D Reines

Publications and source records attributed to H D Reines.

At least 19 recordsLinked to original sources
PubMed1995

A second large controlled clinical study of E5, a monoclonal antibody to endotoxin: results of a prospective, multicenter, randomized, controlled trial. The E5 Sepsis Study Group.

OBJECTIVE: To evaluate the safety and efficacy of E5, a murine, monoclonal antibody directed against endotoxin, in the treatment of patients with Gram-negative sepsis. DESIGN: A multicenter, randomized, double-blind, placebo-controlled trial. SETTING: Fifty-three hospitals across the United States, including university medical centers, Veterans Affairs Medical Centers, and community hospitals. PATIENTS: 847 patients were randomized into this study. Enrolled patients met criteria for three conditions: a) known or suspected Gram-negative infection; b) clinical evidence of sepsis; and c) signs of end-organ dysfunction. Patients with refractory shock were excluded from the study. INTERVENTIONS: Two doses of E5 (2 mg/kg/day by intravenous infusion 24 hrs apart), or placebo that was identical in appearance were administered. In addition, all patients received standard supportive therapy and broad-spectrum antibiotics. MEASUREMENTS AND MAIN RESULTS: The primary end point was mortality over 30 days. Secondary outcome measures included the resolution and prevention of organ failure in the same two populations. Additionally, the safety of E5 was evaluated. There was no significant improvement in survival over 30 days among patients with Gram-negative sepsis who received E5 compared with those patients who received placebo (n = 530; p = .21). In addition, E5 did not improve survival for patients with Gram-negative sepsis and organ failure (n = 139; p = .3). However, a significantly greater percentage of patients with Gram-negative sepsis experienced resolution of major organ failure if they received E5, compared with those patients who received placebo (n = 139; 48% E5 vs. 25% placebo; p = .005). This result extended to all patients who entered the study with one or more major organ failures, regardless of the etiology of the infection (n = 225; 41% E5 vs. 27% placebo; p = .024). E5 also provided protection against the development of some organ failures, but significant prevention was only observed for adult respiratory distress syndrome (p = .007) and central nervous system dysfunction (p = .050). Hypersensitivity reactions attributable to E5 occurred in 2.6% of patients. An asymptomatic antibody response occurred in 44% of the E5-treated patients and in 12% of the patients who received placebo. CONCLUSIONS: In this study, E5 did not reduce mortality in nonshock patients with Gram-negative sepsis whether or not those patients also had organ failure. However, E5 did result in greater resolution of organ failure in patients with Gram-negative sepsis. This benefit extended to those patients with suspected Gram-negative etiology. This finding is important because patients with suspected Gram-negative sepsis and organ failure can be identified without waiting for culture results. In addition, E5 resulted in the prevention of adult respiratory distress syndrome and central nervous system organ failure. However, more studies are needed to determine if this result can be extended to organ failure in general. E5 is safe as a treatment for patients with Gram-negative sepsis.

Antibodies, Monoclonal↗
PubMed1993

Prostaglandins, thromboxanes, leukotrienes, and cytochrome P-450 metabolites of arachidonic acid.

Arachidonic acid is metabolized via three major enzymatic pathways: cyclooxygenase, lipoxygenase, and cytochrome P-450. The cyclooxygenase pathway gives rise to the prostaglandins and thromboxane A2. The lipoxygenase pathway produces the leukotrienes and 5-, 12-, and 15-hydroxyeicosatetraenoic acids. The cytochrome P-450 pathway metabolites are oxygenated metabolites of arachidonic acid. Synthesis of several of the cyclooxygenase and lipoxygenase metabolites are increased in circulatory shock. A potential role for several of these compounds in the pathophysiologic sequelae of endotoxic and septic shock has been implied from a combination of animal and human studies. There are no studies that have explored a potential role for cytochrome P-450 metabolites in the pathogenesis of circulatory shock.

Animals↗
PubMed1992

Stress ulcers and organ failure in intubated patients in surgical intensive care units.

This study compared prophylactic administration of either intragastric misoprostol (200 micrograms four times a day), a prostaglandin E1 analog, or bolus intravenous cimetidine (300 mg every 6 hours) in preventing stress lesions and stress bleeding in 127 adult postoperative patients who required mechanical ventilation and also had developed hypotension or sepsis. Both drug treatments were equally effective in preventing the development of diffuse gastritis (greater than 10 gastric hemorrhagic lesions) and in preventing upper gastrointestinal hemorrhage (UGIH). The combined data from both groups showed that for the 44 (35%) patients who died, death was significantly associated with the presence at study entry of renal failure (64% of 25 patients with renal failure died), hepatic failure (57% of 23 patients) or coagulopathy (62% of 29 patients) (p less than 0.02 for each), and with the number of organ system failures at study entry (48% of 69 patients with multiple organ system failures died, p less than 0.001). Death was also significantly associated with the presence of adult respiratory distress syndrome (ARDS) at study entry or the development of ARDS (63% of 24 patients with ARDS died, p less than 0.001), and the development of UGIH (5% of 93 patients with known bleeding outcome died, p less than 0.05). The number of stress lesions that developed was significantly associated with subsequent UGIH (p less than 0.001). Additional organ system failure developed during the study in 31% of the 127 patients, as did diffuse gastritis in 20% of 111 patients who had a follow-up endoscopy. These results demonstrate that postoperative patients who require mechanical ventilation and have hypotension or sepsis are at significant risk for the development of stress gastric lesions and multiple organ system failure even when prophylaxis for stress ulcers is provided. Furthermore, the presence of ARDS, renal failure, hepatic failure, coagulopathy, and UGIH are significantly associated with death.

Cause of Death↗
PubMed1992

Lactic acidosis treated with continuous hemodiafiltration and regional citrate anticoagulation.

OBJECTIVE: To evaluate the effectiveness of continuous arteriovenous hemodiafiltration (CAVHD) using citrate as the anticoagulant for the treatment of lactic acidosis in patients with renal failure. DESIGN: Case series with careful monitoring of the clinical course of patients being treated in a medical or surgical ICU. SETTING: University hospital ICU. PATIENTS: Two patients with lactic acidosis are described, along with our experience using CAVHD and citrate in other clinical settings. INTERVENTIONS: CAVHD was used to manage renal failure, while a continuous infusion of citrate was administered to maintain patency of the extracorporeal circuit. MEASUREMENTS: Total and ionized serum calcium concentrations and citrate concentrations were monitored. MAIN RESULTS: CAVHD with citrate as the anticoagulant proved to be a convenient means of managing vascular volume, serum electrolyte concentrations, acid-base balance, and replacement renal function requirements in the setting of severe lactic acidosis, oliguric renal failure, and hemorrhagic diathesis. CONCLUSIONS: CAVHD with citrate as the anticoagulant can be recommended as effective therapy for selected patients, but careful monitoring is needed to avoid serious complications.

Acidosis, Lactic↗
PubMed1991

Prostacyclin and thromboxane A2 formation is increased in human sepsis syndrome. Effects of cyclooxygenase inhibition.

Arachidonic acid metabolites, especially thromboxane-A2 and prostacyclin, have been shown to be increased in experimental models of sepsis and the adult respiratory distress syndrome (ARDS) and play a major pathophysiologic role. This study was designed to determine if these metabolites are increased in human sepsis syndrome and if inhibition of fatty acid cyclooxygenase affects their formation and their pathophysiologic sequelae. We conducted a double-blind, placebo-controlled trial of ibuprofen (800 mg given rectally every 4 h for three doses) in 30 patients with sepsis syndrome defined by abnormal vital signs, the appearance of serious infection, and at least one major organ failure. Urinary concentrations of the metabolite of thromboxane-A2, 2,3-dinor-TxB2, and prostacyclin, 2,3-dinor-6-keto-prostaglandin F2 alpha, were elevated 10 to 20 times normal and declined to four to five times normal by 12 h after entry in the ibuprofen-treated group and remained elevated in the placebo-treated patients. The urinary concentration of TxB2 and 6-keto-prostaglandin F1 alpha, which reflect renal production of TxA2 and prostacyclin, respectively, were also increased approximately 10-fold over normal and were subsequently decreased by ibuprofen. Coincident with the reduction in metabolite levels, the ibuprofen-treated group, but not the placebo-treated group, experienced a significant decline in temperature, heart rate, and peak airway pressure, and a trend towards more rapid reversal of shock (p = 0.12).(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclooxygenase Inhibitors↗
PubMed1991

Effect of a LTD4 receptor antagonist in porcine septic shock.

The effect of a selective LTD4 receptor antagonist SK & F104353 was studied in septic pigs anesthetized with isoflurane. Yorkshire pigs (25.2 +/- 2.3 kg) were instrumented and monitored for cardiac output (CO), mean arterial pressure (MAP), systemic vascular resistance (SVR), mean pulmonary arterial pressure (MPAP), pulmonary vascular resistance (PVR), renal artery blood flow (RABF), renal vascular resistance (RVR), arterial PO2, and extravascular lung water (EVLW). Blood samples were also collected for platelet, white blood cell and hematocrit determinations and plasma was assayed for thromboxane (TX) B2. Sepsis was induced by infusion of Pseudomonas aeruginosa (3 x 10(8) CFU%kg/h) for 2 h. Cardiovascular and hematologic data were determined at 30 min intervals for 4 h. Groups were infused with either SK & F104353 (3 mg/kg/h; n = 5) or drug vehicle (n = 6) beginning 15 min prior to infusion with the P. aeruginosa. In the vehicle group beginning at -90 min after sepsis induction, there was a 30 +/- 7% decrease of CO, a 27 +/- 5.0% decrease of MAP, and a 44 +/- 7% decrease of RABF, whereas, MPAP increased to 147 +/- 37% and plasma TXB2 increased from less than 200 pg/ml to 3,049 +/- 367 pg/ml (P less than 0.05). The EVLW and hematocrit increased (P less than 0.05), and the arterial PO2, white blood cell count, and platelet count decreased with the severity of the sepsis. In pigs pretreated with SK & F104353 the MAP and RABF were transiently improved (P less than 0.05), and the decrease in arterial PO2 was delayed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Noninvasive estimation of extravascular lung water using bioimpedance.

Currently, accurate measurements of extravascular lung water (EVLW) are obtained using the double dye dilution technique (DD). However, this method is invasive and complicated and has limited its clinical use. The purpose of this study was to develop a noninvasive method for determining changes in EVLW using bioimpedance (BI) and compare these measurements with DD in a model of acute pulmonary injury. Nine adult dogs were anesthetized and instrumented with a pulmonary artery and an EVLW arterial catheter with EVLW-DD and cardiac output calculated from the dye and thermal dilution curves. Eight external electrodes were placed on the thorax and impedance changes were measured by computer. Changes in EVLW-BI were computed as a function of the thoracic volume and impedance. Cardiac output (CO) from BI was obtained by electronically differentiating the bioimpedance signal. EVLW and CO were measured using DD and BI at 0, 15, 30, and 60 min following injection of oleic acid (0.1 cc/kg). Changes in EVLW were correlated over all time periods using DD and BI (r = 0.70, P less than 0.05); however, several impedance EVLW estimates varied greatly from double dilution methods. There was no difference in computed EVLW using DD and BI at 15, 30, and 60 min following oleic acid infusion (P greater than 0.35). CO was significantly correlated using DD and BI (r = 0.81, P less than 0.05). In summary, bioimpedance may hold promise as a noninvasive and continuous means for estimation of EVLW in the critical care setting.

Animals↗
PubMed1989

Conventional versus high frequency jet ventilation with a bronchopleural fistula.

A bronchopleural fistula (BPF) is an aberrant pathway through which inspired gas exits the lungs. A BPF may cause significant respiratory compromise, which in turn may result in the need of mechanical ventilation. The purpose of this study was to compare the efficacy of conventional positive pressure ventilation (CV) with high frequency jet ventilation (HFJV) using increasing increments of positive end expiratory pressure (PEEP) in the management of an induced BPF. A reproducible model of a BPF was surgically created in 10 mongrel dogs. Measurements of blood pressure (BP), cardiac output (CO), mean airway pressure (Maw), peak airway pressure (Paw), and fistula flow (FF) were carried out with the chest closed. Selective occlusion of the BPF allowed for blood gas stabilization at increased values of PEEP. Paired observations were performed at 0, 5, 10, 15, and 20 cm H2O of PEEP, while maintaining PaCO2 between 30 and 50 Torr. There was no difference in BP or CO between ventilation methods even though significantly lower Maw and Paw pressures were obtained using HFJV. While FF increased significantly with each increment of PEEP, there was no improvement in flows obtained using HFJV. This acute model of a BPF demonstrated that increasing PEEP dramatically increases FF irrespective of the method of ventilation.

Animals↗
PubMed1989

A prospective comparison of IMV and T-piece weaning from mechanical ventilation.

Two hundred (200) consecutive medical and surgical patients requiring mechanical ventilation were entered into a prospective randomized trial of weaning by either intermittent mandatory ventilation (IMV) or T-piece. Patients in these groups were of similar age and sex and had the same total ventilation time (TVT). The study design provided equal time for each weaning mode after specific criteria for oxygenation and ventilation were satisfied (PaO2 greater than 55 mm Hg on FIO2 less than 0.5; VE less than 12 L/min and two of the following four parameters: MVV greater than 2 VE, VT greater than 5 ml/kg, FVC greater than 10 ml/kg, NIF less than or equal to -20 cm H2O). Of the original 200 patients 165 were entered into the weaning phase; 35 patients were withdrawn prior to weaning due to the discretion of the attending physician or protocol error. Weaning time was not different between the IMV (5.3 +/- 1.2 h, mean +/- SEM) and T-piece groups (5.9 +/- 1.4 h, p = NS). Of the 165 patients, 155 (93 percent) were weaned successfully by protocol, 79 in the IMV and 76 in the T-piece group. Of 155 patients, 136 (88 percent) were weaned on the first attempt by protocol. Of the 19 who were not weaned, 11 were weaned successfully on the second and five on the third trial; three patients required three-day weans. We conclude that clinically stable patients who require short-term mechanical ventilation and meet standard bedside weaning criteria can be weaned efficiently by protocol using either IMV or T-piece techniques.

Adult↗
PubMed1989

The rat in sepsis and endotoxic shock.

Compared to the experimental studies, interpretation of eicosanoid levels in human sepsis is complicated by a large number of uncontrolled variables. Further clinical studies are needed to establish the relationship between the septic rat model and the human septic condition. The rat model is useful for uncovering fundamental pathophysiologic processes and should be useful in developing therapeutic interventions in human circulatory shock. Studies on the rat model offered the first indication that eicosanoids were involved in the shock syndrome (Cook et al., 1980). This led to clinical trials to determine the role of these mediators in human sepsis (Reines et al. 1982). The rat affords a model system which allows for pharmacologic manipulation and testing of a large number of hypotheses in a practical and cost effective manner. The recent evidence that leukotrienes are released during circulatory shock in the rat and that attenuation of this release alters the pathophysiologic outcome (Ball et al., 1986), lays the groundwork for future clinical studies. Finding that eicosanoids and leukotrienes are elevated in rat models of adult respiratory distress syndrome (Hammarstrom, 1983) has opened further new areas of clinical inquiry. Although rat models involving bolus endotoxin administration have not been predictive of the human septic syndrome, they have proven useful in the determination of the cellular sources and mechanisms of eicosanoid and leukotriene action. From the evidence presented, the septic shock rat model would seem to be the best model in predicting the outcome of therapies in human sepsis. Limited clinical trials have assessed the therapeutic efficacy of pharmacologic agents which alter eicosanoid and leukotriene metabolism in sepsis. In view of the continued high mortality of patients with septic shock and the failure of conventional therapies (Sprung et al., 1984; DuToit et al. 1985), further clinical and experimental studies are desirable.

Adrenal Cortex Hormones↗
PubMed1988

Complications of nasoenteric feeding tubes.

Small-bore, silicone nasoenteric feeding tubes are increasingly utilized in the critically ill patient to provide nutritional support. The metallic-weighted tips and stiffening introducing stylets create the potential for misplacement with potentially serious consequences. We have reported our experience with 14 patients who had inadvertent tube misplacement, resulting in complications that included pneumothorax, hydrothorax, empyema, mediastinitis, pneumonia, and esophageal perforation. The incidence of radiographically detected abnormal tube position was 1.3 percent. The presence of cuffed tracheostomy or endotracheal tubes did not prevent this occurrence. The institution of enteral feedings should, therefore, be performed according to strict guidelines which include radiographic confirmation of desired position before feedings are initiated, limited and supervised use of stylets, and a need for special precautions in patients who are obtunded or receiving intubated respiratory assistance.

Aged↗
PubMed1988

Comparison of bioimpedance and thermodilution methods for determining cardiac output: experimental and clinical studies.

The changes in electrical bioimpedance caused by the blood flow through a thoracic segment may be measured using a series of electrodes placed at opposing ends of this segment. Cardiac output (CO) is calculated by computer as the change in bioimpedance over time. This study was performed to determine the accuracy of bioimpedance CO (CObi) compared with standard thermodilution CO (COtd) in an animal model and in patients. COtd was determined using a thermodilution CO computer, and CObi was calculated with a bioimpedance computer in 10 dogs at baseline and at 5-minute intervals following the injection of 7 mEq of calcium chloride. A high correlation between COtd and CObi was observed (r = 0.91, p less than 0.001) over a range of 2.5 to 6 L/min. Thirty-three paired observations using the CObi and COtd methods were performed in 10 patients following elective coronary artery bypass surgery. A significant correlation between the two methods was determined with a CO range of 2.1 to 7.8 L/min (r = 0.77, p less than 0.001). CObi became inaccurate with severe tachycardia (pulse, 180/min), low CO, or frequent arrhythmias. These results indicate that this technique provides a continuous noninvasive method of determining CO that is comparable with thermodilution techniques. The technique of CObi holds promise for widespread use when continuous and noninvasive monitoring of CO is necessary.

Adult↗
PubMed1988

A new device for emergency percutaneous transtracheal ventilation in partial and complete airway obstruction.

Several methods of percutaneous transtracheal ventilation have been described for the immediate relief of upper airway obstruction when conventional methods fail. This study was conducted to determine whether a single percutaneously placed catheter introducer (Arrow Emergency Infusion Device [EID]) could provide access adequate for percutaneous transtracheal ventilation with standard ventilatory modalities in an obstructed airway. Ten mongrel dogs were anesthetized, intubated, and monitored (for pulse, blood pressure, ECG, and arterial blood gases). The endotracheal tube was occluded. When the dogs became hypoxic and hypercarbic, the Arrow EIDs were inserted transtracheally and the dogs were ventilated with either a Bear 1 Adult Ventilator or a Mapleson D system. Percutaneous transtracheal ventilation by the Arrow EID adequately ventilated dogs with controlled partial (95%) or complete airway obstruction from hypoxic and hypercarbic states. The ease of insertion, decreased associated complications, ability to ventilate with easily available devices, and use with complete airway obstruction make the EID an effective device for transtracheal ventilation.

Airway Obstruction↗
PubMed1988

Resuscitative thoracotomy: the effect of field time on outcome.

In the past 5 years, 72 moribund patients have undergone resuscitative thoracotomy (RT) at the Medical University of South Carolina: 62 patients underwent the procedure before the adoption of a policy of mandatory rapid transport (scoop and run) for penetrating and unstable victims of trauma by our EMS system (Group I). Group II is comprised of ten patients who underwent RT following adoption of this policy. Resuscitation was successful in three patients in Group I (4.8%) and there were only two survivors (3.2%). In contrast, resuscitation was successful in two of ten patients in Group II (20%) and there was one survivor (10%). Nineteen patients in Group I (31%) were in traumatic full arrest on the scene, all of whom died. Twenty-five patients in Group I (40%) had a measureable pulse and/or blood pressure when EMS personnel arrived at the scene and subsequently "died" before their arrival at the trauma center. RT was also uniformly unsuccessful in this subgroup. Eighteen patients in Group I (29%) suffered cardiac arrest following their arrival at the hospital. Three of these patients (16.6%) were successfully resuscitated and two (11%) survived to leave the hospital. There were four traumatic full arrests in Group II (40%) and all four died. Only two patients in Group II (20%) lost their vital signs in transport and both died. Four patients in Group II (40%) suffered cardiac arrest after arrival at the hospital. Two of these patients (50%) were successfully resuscitated and one left the hospital (25%).(ABSTRACT TRUNCATED AT 250 WORDS)

Emergency Medical Services↗
PubMed1988

Is advanced life support appropriate for victims of motor vehicle accidents: the South Carolina Highway Trauma Project.

There is continuing controversy over the use of Advanced Life Support (ALS) in the treatment of multisystem injury. In this study, performed to define the role of ALS in the management of motor vehicle accidents (MVA), 538 ambulance run reports (ARR) and hospital records of patients involved in MVA in South Carolina for 1983 were examined. Of these, 248 were reviewed in depth by a trauma review committee (TRC). Paramedics were present in 81% (93% urban, 80% rural) of cases. ALS crews averaged 24.8 minutes on the scene compared to 18.1 minutes for Basic Life Support (BLS). It took 6 minutes longer to transport rural patients than urban patients (15.7 vs. 9.6 min). Total EMS time (response, on scene, transport) was 46 +/- 20 minutes. Extrication increased on-scene time from 20.5 to 31.1 minutes. Endotracheal intubation attempts were 67% successful and IV's were placed in 88% of attempts. Thirty-two per cent of ALS patients demonstrated an increased blood pressure en route compared to 12% of BLS patients. The TRC felt prehospital care was beneficial in 85% of cases, while 11.7% had inappropriate or inadequate care. Resuscitation and ALS in MVA appears to be beneficial in the treatment of multisystem trauma in a rural state.

Accidents, Traffic↗