Complications In High-risk Patients Research Articles

An overview of the results of clinical trials with glycoprotein IIb/IIIa inhibitors

The era of platelet glycoprotein (GP) IIb/IIIa receptor inhibition in cardiology was inaugurated in 1994 with the publication of the Evaluation of 7E3 for the Prevention of Ischemic Complications (EPIC) trial results. EPIC demonstrated that the GP IIb/IIIa blocker abciximab, administered as a bolus and 12-hour infusion, afforded protection against ischemic complications in high-risk patients undergoing angioplasty and atherectomy, including those with unstable angina or evolving myocardial infarction (MI). A significant reduction in the incidence of death, acute MI, or revascularization was apparent at 30 days and also sustained at 6-month and 3-year follow-up. The subsequent Evaluation in PTCA to Improve Long-Term Outcome with Abciximab GP IIb/IIIa Blockade (EPILOG) study extended these findings to the full spectrum of coronary intervention patients, confirming that abciximab provided similar benefits in low-risk patients as well. The EPILOG trial also proved that any excess bleeding risk associated with potent antiplatelet therapy could be brought down to placebo levels through the use of a low-dose, weight-adjusted heparin regimen, early vascular sheath removal, and elimination of routine postprocedural heparinization. The potential for an advantage of GP IIb/IIIa blockade in patients with refractory unstable angina/non-Q-wave MI was demonstrated in the c7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina (CAPTURE) trial, which showed that a 24-hour preprocedural abciximab infusion effectively stabilized these patients, thereby enhancing the safety of intervention and reducing the 30-day incidence of ischemic events. A similar pattern of benefit has emerged from clinical trials of such other GP IIb/IIIa inhibitors as eptifibatide, lamifiban, and tirofiban. Trials are currently underway to clarify the benefits of GP IIb/IIIa blockers in patients undergoing stenting and as an adjunct to thrombolytic therapy or primary angioplasty in patients with acute MI (ST-segment elevation). (Am Heart J 1998;135:S43-S55.)

Bivalirudin Compared With Heparin During Coronary Angioplasty for Thrombus-Containing Lesions

Objectives. We investigated whether bivalirudin is more effective than heparin in preventing ischemic complications in high risk patients undergoing coronary angioplasty for thrombus-containing lesions detected by angiography.Background. Heparin is administered during coronary angioplasty to prevent closure of the dilated vessel. Bivalirudin (Hirulog) is a direct thrombin inhibitor that can be safely substituted for heparin during angioplasty. Bivalirudin has several theoretic advantages over heparin as an anticoagulant agent.Methods. We performed an observational analysis of the Hirulog Angioplasty Study in which 4,098 patients with unstable or postinfarction angina were randomized to receive either bivalirudin or heparin during coronary angioplasty. The study group for this analysis consisted of 567 patients who had thrombus-containing lesions on angiography. The primary end point was death, myocardial infarction, emergency coronary artery bypass graft surgery or abrupt vessel closure before hospital discharge.Results. Patients with thrombus-containing lesions had a higher incidence of myocardial infarction (5.1% vs. 3.2%, p = 0.03) and abrupt vessel closure (13.6% vs. 8.3%, p < 0.001) than those without thrombus. In patients with thrombus-containing lesions, however, the incidence of the primary end point was not different between the bivalirudin and heparin treatment groups. Furthermore, no difference in the incidence of ischemic events at 6 months was seen between the treatment groups.Conclusions. Bivalirudin is not more effective than heparin in preventing ischemic complications in patients undergoing coronary angioplasty for thrombus-containing lesions detected by angiography. Other approaches, perhaps involving potent antiplatelet agents, should be considered for patients with thrombus-containing lesions.

4.8 Flat reduction of postoperative complications in high-risk patients who underwent CABG without cardiopulmonary bypass (CPB)

CO2 and holmium:yttrium aluminum garnet (YAG) transmyocardial laser revascularization (TMLR) are used to treat patients with refractory angina. A randomized trial to investigate the efficacy and safety of XeCl excimer TMLR was performed.Thirty patients with refractory angina were randomized in pairs to excimer TMLR or maximal medication. We assessed angina, quality of life (QOL), exercise time, myocardial perfusion, and ventricular wall motion at base line and at 3, 6, and 12 months after TMLR.TMLR patients manifested a significantly better outcome with respect to angina class and quality of life. One TMLR patient died perioperatively versus none in the control group. After TMLR angina decreased from class 3.8 ± 0.4 at base line to 1.9 ± 0.9 at 12 months versus 3.9 ± 0.3 to 3.7 ± 0.6 in the control group, respectively (p = 0.000001). At 12 months a decrease of greater than or equal to two angina classes was indicated in 11 out of 14 TMLR patients versus none in the control group (p = 0.00001). Improved myocardial perfusion or exercise time was not indicated despite a small decrease in reversible wall motion abnormality score.Excimer TMLR significantly relieves angina and improves QOL without evidence of improved cardiac perfusion or function.

Doppler velocimetry of intraplacental fetal vessels in the second trimester: improving the prediction of pregnancy complications in high-risk patients.

The purpose of our study was to assess the value of fetal intraplacental velocimetry in predicting adverse pregnancy outcome in high-risk patients. Thirty-two women with pregnancies of 22 to 25 weeks' gestation were evaluated. They had demonstrated abnormal first-trimester Doppler characteristics, yet had normal second-trimester umbilical artery velocimetry. Doppler waveforms were obtained and the ratio between intraplacental and umbilical artery resistance indices was calculated. Abnormally high ratios of intraplacental to umbilical artery resistance indices were associated with a significantly higher incidence of pregnancy complications. Among women with abnormal ratios, 17 (80%) of 21 pregnancies had later complications, whereas among those with normal ratios, only two (18%) of 11 women experienced later complications. This study demonstrates that analysis of the ratio between intraplacental and umbilical artery resistance indices in the second trimester improves the diagnostic value of Doppler velocimetry in pregnancies at risk for later obstetric complications.

A Fixed-Dose Combination of Low Molecular Weight Heparin with Dihydroergotamine versus Adjusted-Dose Unfractionated Heparin in the Prevention of Deep-Vein Thrombosis after Total Hip Replacement

The low dose heparin regimen (LDH) is not appropriate for prevention of intra- and postoperative thromboembolic complications in high risk patients, especially those undergoing elective hip replacement. Despite LDH prophylaxis, the incidence of deep-vein thrombosis (DVT) remains in a range of 20 to 35%. Adjusted-dose unfractionated heparin prophylaxis is thought to be one of the most effective regimens for thrombosis prophylaxis in this indication, but it requires two or three daily injections as well as precise monitoring of the activated partial thromboplastin time (aPTT). As an attractive alternative, we investigated the efficacy and safety of the low molecular weight heparin (LMWH) certoparin combined with dihydroergotamine (DHE) given once daily. In a randomised, open clinical trial, a total number of 305 patients undergoing total elective hip replacement were enrolled and divided into two groups, either receiving a fixed-dose combination of LMWH (3,000 IU) and DHE (0.5 mg) subcutaneously once daily, or adjusted-dose unfractionated heparin (UFH) subcutaneously every 8 h. The UFH dosage was adjusted daily to keep an aPTT of about 50 s. The aPTT was determined 3 h after the morning injection. During the study, the starting dose (15,000 IU/day) was increased to a plateau value of 28,800 +/- 7,150 IU/day (mean +/- SD) to maintain the aPTT in the prescribed range. The plateau value was achieved after 8 postoperative days. For analysis of efficacy 289 patients were evaluable. The occurrence of deep vein thrombosis was determined by bilateral ascending venography, which was performed on the same day in patients with clinical signs suggesting DVT; and in all remaining patients at the end of the prophylaxis period. Deep vein thrombosis was diagnosed in 17 of 142 patients (12.0%) treated with LMWH/DHE and in 13 of 147 patients (8.8%) treated with adjusted-dose UFH. Combined distalproximal thrombosis was more frequently in patients receiving UFH (n = 5; 3.4%) compared to the LMWH/DHE group (n = 2; 1.4%). These differences are statistically not significant. In the UFH group one case of non-fatal pulmonary embolism occurred. Both prophylaxis regimens were well tolerated; wound bleeding was observed in 8 (5.3%) patients in the LMWH group and in 6 (4.0%) patients in the UFH group. Intraoperative blood-loss volume (mean +/- SD) was 751 +/- 339 mL (LMWH/DHE) and 736 +/- 380 mL (UFH), whereas postoperative drain-loss volume (mean +/- SD) was found to be 523 +/- 333 mL (LMWH/DHE) and 581 +/- 404 mL (UFH). Whole blood transfusion volumes (mean +/- SD) were 570 +/- 202 mL (LMWH/DHE) and 748 +/- 455 mL (UFH). Additionally, red cell replacement volumes (mean +/- SD) were 804 +/- 435 mL (LMWH/DHE) and 720 +/- 328 mL (UHF). Revision of wound or additional drainage were necessary in 3 LMWH/DHE and 7 UFH patients. One patient needed reoperation due to bleeding, 3 (2.0%) had petechia and 1 exhibited an allergic exanthema, all of them in the UFH group. A slight erythema at the injection site was observed in 6 (3.9%) patients receiving LMWH/DHE. During the course of prophylaxis, injection hematomas were documented in 57.9% (LMWH/DHE) and in 61.4% (UFH) of the patients. All differences were statistically not significant. Single daily subcutaneous injections of LMWH/DHE appeared to be safe and efficacious compared to adjusted-dose UFH for prophylaxis of DVT in high-risk patients.

Myocardial protection for coronary bypass grafting: The Toronto Hospital perspective

The contemporary results of coronary artery bypass grafting using a variety of myocardial preservation techniques are excellent. In recent years, the number of "high-risk" patients referred for operation has increased, thus necessitating continued advances in surgical myocardial protection. In this article, we review recent advances in clinical myocardial protective techniques and emphasize studies conducted at The Toronto Hospital. Further, on the basis of promising current research, we speculate on future prospects for myocardial protection. At The Toronto Hospital, we converted from crystalloid to intermittent cold blood cardioplegia in 1985. We demonstrated that "continuous" cardioplegic strategies may help resuscitate the ischemic myocardium and reduce operative complications in high-risk patients. Further improvements in myocardial protection will require refinements in cardioplegic solution temperature, direction of delivery, and additives to "precondition" the myocardium against ischemic damage. Major advances that meet the requirements of an increasingly high risk patient population have been made in surgical myocardial protection in recent years. The future is bright for continued progress in this area.

Infected Lower Extremity Extra-Anatomic Bypass Grafts: Management of a Serious Complication in High-Risk Patients

To determine optimal management and outcome of infected extra-anatomic bypass grafts (EABG), we reviewed 28 patients (19 men and 9 women; mean age 70 years) treated over a 13-year period. Mean follow-up was 42 months. There were 16 axillofemoral (AF), 10 femorofemoral (FF), and two axillopopliteal (AP) grafts. Risk factors included previous prosthetic graft infection in 13 patients, enterocutaneous fistula in two, and mycotic aortic aneurysm in one. Initial management involved complete graft excision in 12 patients, partial graft excision in 10, and nonresectional therapy in six. Failure of nonresectional therapy and partial excision in three patients each required further operative intervention with graft excision. Reconstruction in patients eventually requiring graft excision (n = 25) entailed placement of a new prosthetic AF or AP graft in eight, an autogenous FF graft in five, combined prosthetic AF and autogenous FF bypass in two, autogenous iliofemoral bypass in one, obturator bypass in one, or no reconstruction in eight. Four autogenous FF reconstructions thrombosed immediately postoperatively, and three prosthetic reconstructions became infected. The mortality rate was 18% (FF = 20%, AF = 19%, AP = 0%). The amputation rate was 25% (AP = 100%, AF = 25%, FF = 10%) and was higher without arterial reconstruction (56% vs. 12%, p = 0.02). Two patients required hemipelvectomies and one had bilateral hip disarticulation. We conclude that EABG infections can be successfully treated but carry significant morbidity and mortality. Optimal management includes EABG resection and prompt revascularization, bearing in mind the risk of early thrombosis in autogenous grafts and reinfection in prosthetic grafts.

“Unexplained” Delayed Death From Fungal Meningitis After Meningioma Resection

Progressive deterioration and ensuing death following a neurosurgical procedure often represents a diagnostic challenge to the team responsible for patient care. Many, but not all, causes are treatable if a diagnosis is made early. A 69-year-old woman who died 6 weeks post-operatively following a meningioma resection is reported. An initial routine post-operative course became complicated by progressive neurological deterioration 3-4 weeks later. Despite extensive investigation she died 6 weeks post-operatively without a diagnosis. Autopsy demonstrated extensive Candida meningitis. A review of the literature demonstrates this to be a reported complication in high risk patients, difficult to diagnose, but treatable when identified. Fungal meningitis should be high in the differential diagnosis in the post-operative patient with delayed, unexplained neurological deterioration, especially when associated with negative CSF cultures.

Value of different non-invasive methods for the recognition of arrhythmogenic complications in high-risk patients with sustained ventricular tachycardia during programmed ventricular stimulation.

It is well known that patients with coronary heart disease and ventricular tachycardia show a high incidence of arrhythmogenic complications and sudden cardiac death. The best predictor of spontaneous ventricular tachycardia and sudden death in these patients is programmed ventricular stimulation, but this invasive method is limited to specialized institutions. The purpose of our study was to assess the predictive value of Holter monitoring, late potentials and heart rate variability as markers for these high-risk patients. We investigated 20 patients (18 m, 2 f, age range 31-79 years) with coronary artery disease documented angiographically (6 patients with single vessel disease (vd), nine patients with 2 vd, five patients with 3 vd) and previous myocardial infarction. Each patient underwent 24-h ambulatory monitoring with analysis of rhythm of heart rate variability (24-h spectral and non-spectral analysis) and a signal-averaged ECG with late potential measurement. In all patients, sustained ventricular tachycardia was inducible during programmed ventricular stimulation. Late potentials were recorded in 12 out of the 20 patients (60%). Ventricular arrhythmias of Lown classes IVa, IVb or V were recorded in 12 patients. Analysis of heart rate variability compared to 20 age- and sex-matched healthy controls revealed a loss of parasympathic activity and increased sympathic activity in 16 of the 20 patients (80%). in this study, heart rate variability was the most sensitive method with which to recognize patients at a high risk of arrhythmogenic complications. Evaluation of the above parameters in large controlled clinical trials may help predict arrhythmogenic complications and sudden cardiac death.

A cost-utility analysis of preoperative total parenteral nutrition.

It has been suggested that preoperative total parenteral nutrition may be used to reduce the risk of nutrition-associated postoperative complications in high-risk patients. These patients can be identified based on their nutritional status. The efficiency of this intervention is assessed using the technique of cost-utility analysis. Data from multiple sources is integrated to perform the economic assessment. The cost-utility ratios for treating several malnourished patients with localized upper gastrointestinal cancer are below $40,000. These cost-utility ratios compare favorably with published results of other programs. The ratios increase considerably if patients who are better nourished (at lower risk of postoperative complication) receive the intervention. The analysis is very sensitive to the efficacy of the intervention.

Pneumothorax due to nasogastric feeding tubes. Report of four cases, review of the literature, and recommendations for prevention

Intrapulmonary placement of small-bore nasogastric feeding tubes caused pneumothoraces in four patients. Review of the literature discloses another 106 cases of the same complication. Risk factors for intrapulmonary complications include endotracheal intubation or tracheostomy (60% of reported cases [95% confidence interval, 44% to 80%]), and altered mental status (36% of reported cases [95% confidence interval, 24% to 53%]). We propose a simple, two-step method of feeding tube insertion designed to prevent such complications in high-risk patients.

Peptic ulcer complications in high-risk patients.

AbstractDistinct groups of patients at high risk for the development of peptic ulceration of the stomach and duodenum have been identified. As newer forms of treatment for critical illness evolve, it seems probable that other high‐risk groups will be described. The etiology of the ulcerations appear to be different for each group. The presence of intraluminal acid is correlated with the incidence of bleeding. Acid‐reducing therapy, whether intraluminal or intravenous, is effective in decreasing the risk of bleeding to variable degrees among the high‐risk groups but does not prevent or reduce the incidence of ulceration. When surgical therapy is needed, no operation is superior.

Clinical applications of antiviral agents for chemophrophylaxis and therapy of respiratory viral infections

SummaryTable III summarizes clinical applications of antiviral agents in respiratory viral infections. Table IIIClinical Applications of Antiviral Agents in Respiratory Viral InfectionEffective forVirusProphylaxisTreatmentInfluenza AAmantadine (oral)Amantadine (oral)*Rimantadine (oral)Rimantadine (oral)*Ribavirin (aerosol)*Influenza BRibavirin (aerosol)*Resp. syncytialRibavirin (aerosol)RhinovirusIFN-a2 (intranasal)*Efficacy has been established only in uncomplicated diseaseFor influenza A virus infections, both oral amantadine and rimantadine are effectvive when used for seasonal prophylaxis and for prophylaxis in institutional populations. Both of these drugs, as well as aerosilized ribavirin, have antiviral and therapeutic effects in uncomplicated influenza. It remains to be determined whether any of these modalities or possibly their combined use [44] will be useful in treating severe influenza in hospitalized patients or whether they can prevent the development of complications in high risk patients. Unfortunately, there is no parenteral formulation of amantadine or rimantadine for use in critically in patients.Aerosolized ribavirin has also been shown to have modest therapeutic effects in influenza B virus infection. However, a major need exists for an antiviral which is active against influenza B virus and which can be used on an outpatient basis. Controlled clinical trials have shown that aerosolized ribavirin therapy improves arterial oxygenation and modifies the severity fo respiratory syncytil virus bronchiolitis and pneumonia [3,5]. Its role in treatinglife-threatening disease or in dodifying the long-term sequelae of RSV infections are unknown at the present time. Again, a specific antiviral agent is needed for out-patient use in preventing or treating RSV infections.Finally, after over a decade of work since the original observation that intranasal interferon could prevent experimental rhinoirus infection [11], recent studies have established that intranasal rIFN-a2 is effective in the postexposure prophylaxis of rhinovirus colds in families [42]. This strategy needs to be studied with regard to the prevention of infection and its complications in high risk patients and it remains to be determined whether intranasal interferen will have therapeutic activity in established colds.

Empiric antimicrobial therapy in cancer patients.

The majority of fevers which occur in granulocytopenic cancer patients appear to have an infectious etiology [1]. The practice of initiating empiric antibiotic therapy when the granulocytopenic cancer patient becomes febrile is now well established and has markedly reduced the early morbidity and mortality of infections in these patients. Nonetheless, infections still remain the leading cause of death in neutropenic cancer patients, necessitating refinements in the diagnosis and management of the complications in high risk patients.

Infectious complications in the child with cancer. III. Prevention

BECAUSE IN Ff~CTiON is the major cause of death in the patient with cancer, considerable attention has been focused on methods for preventing'infectious complications in high-risk patients. This requires a thorough understanding of the factors that heighten the risk for serious infection, including disease- and treatment-related defects of the integumentary and mucosal physical barriers, diminished phagocytic defenses, decreased cellular and humoral immunity, and nutritional deficiency. More than 80% of the infections which occur in the patient with cancer are caused by microorganisms resident in the patient's flora; nearly half of these infecting organisms are acquired by the patient during hospitalization (the most frequent nosocomial isolates are Ps. aeruginosa, E. coli, K. pneumoniae, and C. albicans). 2~ .24 Hence colonization of the patient by new pathogenic organisms sets the stage for subsequent infectious complications (Fig. 1). Numerous hospital sources contribute to colonization, including staff-to-patient and patient-to-patient transmission, food, air, water, hospital equipment (respirators, vaporizers), and medical and surgical manipulations and procedures. In addition~ the endogenous or acquired microbial flora of the patient can be adversely perturbed by the antibiotics and chemotherapeutic agents frequently employed in cancer treatmentY ~. '-''~ Consequently, a primary objective, during the past 15 years, has been to develop methods to suppress or eliminate the endogenous microbial burden, as well as to decrease the acquisition of new hospital-acquired organisms.

Prevention of Pulmonary Complications in High Risk Patients

With the potential causes of respiratory failure defined in the first article, a rational approach to prevention can be outlined. Van De Water supplies a protocol for pulmonary prophylaxis in the surgical patient—the patient with normal lung function prior to operation. He reminds us of a fact that our English colleagues know well — routine pulmonary prophylaxis is a function of good nursing care. Special attention should be paid to the patient who is at high risk for pulmonary complications. Hechtman and colleagues discuss identification of these patients, taking us from the obvious risk factors, such as obesity and smoking, to the subtle interrelationships of cardiac and pulmonary function in patients already hospitalized with acute disease. Shah and Powers discuss pulmonary prophylaxis in high risk patients. Their article necessarily includes detailed methods of management of respiratory failure.