1. Walters-Fischer, Patricia BS, RN
  2. Trent, Andrea MSN, RN
  3. Mennick, Fran BSN, RN
  4. Chu, Julie J. MSN, CRNP

Article Content


Effective after intensive therapy for hematologic cancers.

A recently published study reports promising results in the use of a new drug, palifermin (Kepivance; a recombinant human keratinocyte growth factor), for the reduction of the duration and severity of oral mucositis after intensive chemotherapy and radiotherapy for hematologic cancers.


From March 2001 to October 2002, 212 patients were randomly assigned in equal numbers to receive either at least one dose of palifermin or placebo. Patients in the palifermin group were given 60 micrograms per kilogram daily, and those in the other group were given placebo intravenously for three consecutive days immediately before the initiation of conditioning therapy and after autologous hematopoietic stem cell transplantation.


The incidence of oral mucositis grade 3 or 4 was seen in 63% of the patients receiving the drug and in 98% of patients in the placebo group (P < 0.001).


Not only were there fewer cases of oral mucositis in the palifermim group, the median duration of the condition was one-third shorter (six days) than it was in the placebo group (nine days), patients used less opiate for pain control (212 mg and 535 mg, median, of morphine equivalents, respectively), and the incidence of the administration of total parenteral nutrition was lower (31% of patients), compared with the placebo group (55% of patients).


Oral mucositis afflicts as many as 75% of patients who undergo intensive chemotherapy and radiotherapy before hematopoietic stem-cell transplantation and 77% of patients with head and neck cancer who receive that treatment. Because the condition causes severe pain and can exacerbate anorexia, degenerate the quality of life, and heighten the risk of the development of septicemia, the study findings are promising. -PWF


Spielberger R, et al. N Engl J Med 2004;351(25):2590-8. Garfunkel AA. N Engl J Med 2004;351(25):2649-51.



Association with perinatal and maternal risk.

A four-year observational multi-center study reports that a trial of labor after prior cesarean section delivery is associated with perinatal and maternal risk that, although low, is greater than that associated with elective repeated cesarean delivery without labor.


From 1999 to 2002, 378,168 babies were born at 19 academic medical centers in the National Institute of Child Health and Human Develop ment Maternal-Fetal Medicine Units Network. Among 45,988 women who had a singleton pregnancy and a history of cesarean delivery, 17,898 attempted vaginal delivery, 15,801 underwent elective repeated cesarean delivery without labor, and of the remaining 12,289 who underwent a repeated cesarean section, the operation was indicated in 9,013. To be classified as undergoing a trial of labor, women had to present in labor with a cervical dilation of at least 4 cm, and those in whom labor was induced by the administration of oxytocin were also so classified.


The women who underwent elective repeated cesarean section without labor and those who had "other indications for a cesarean delivery, such as a prior classical . . . or 'inverted T' incision, breech or transverse presentation, placenta previa, prior myomectomy, [fetal distress,] genital herpes, or a medical condition precluding a trial of labor," were included in the cesarean section group. Among all attempted trials of labor, uterine rupture occurred in 124 (0.7%) and hypoxic ischemic encephalopathy occurred in 12 infants (P < 0.001). Seven of the instances of hypoxic ischemic encephalopathy, two of which resulted in neonatal death, followed uterine rupture, rendering the absolute risk 0.46 per 1,000 women at term undergoing a trial of labor. No hypoxic ischemic encephalopathy occurred among the women who underwent elective repeated cesarean delivery. Interestingly, the women who had successful vaginal deliveries after cesarean section were more likely to have had smaller babies, a prior vaginal delivery after a cesarean section, and only one prior cesarean delivery.


It should be noted that the study reported that among women undergoing a trial of labor and those who had a repeated cesarean section, there were no significant differences in the rates of hysterectomy and maternal death (0.2% and 0.3%, and 0.02% and 0.04%, respectively), but there were slightly lower rates of endometritis in the cesarean section group, compared with the trial of labor group (1.8% and 2.9%, respectively), and of transfusions (1.0% and 1.7%, respectively).


There are risks when a vaginal delivery is attempted after a cesarean section, and this most recent study of the issue finds them to be small but significant. Medical practitioners therefore should inform women of them in discussions of a trial of labor versus a repeated cesarean delivery. -PWF


Landon MB, et al. N Engl J Med 2004;351 (25):2581-9; Greene MF. N Engl J Med 2004; 351(25):2647-9.



Several risk factors independently associated with complication.

A recently published study conducted by researchers in Colombia investigated both the incidence of intraabdominal infection in patients who had sustained abdominal trauma and the risk factors associated with their development.


The prospective study included 762 patients admitted to a level I trauma unit who were at least 12 years of age and had had surgical intervention for blunt or penetrating abdominal trauma. The primary outcome was intraabdominal infection, although other outcomes, such as other hospital-acquired infection and death, also were evaluated. Several variables, such as the extent of the injury, as assessed according to the Abdominal Trauma Index, the Revised Trauma Score, and the Injury Severity Score, the number of abdominal quadrants contaminated, the use of preoperative antibiotics, blood transfusion requirements, and others, were analyzed during each stage of surgery-preoperative, intraoperative, and postoperative.


The results revealed that the incidence of intraabdominal infection was 10.6%, afflicting 81 of the 762 patients, and that the majority of infections involved peritonitis (51.9%), the next most common being intraabdominal abscess (42%). Each operative stage was associated with several risk factors that bore an association with intraabdominal infection. Preoperatively, wounds from gunshots and blunt trauma, the absence of prophylactic antibiotics, and higher scores on the various trauma scales were identified with the risk of infection. Intraoperatively, factors included procedures that lasted longer than two hours, systolic hypotension, abdominal contamination, and the receipt of blood transfusion. Postoperatively, ICU admission, the presence of surgical packing, and an open abdomen were among the associated variables.


The researchers applied a multivariate analysis to reveal three risk factors, in particular, that yielded an independent association with intraabdominal infection-an ATI score of 25 or higher, the presence of abdominal contamination, and the necessity of ICU admission. The authors caution, however, that those factors alone are not sufficient in predicting intraabdominal infection.


The researchers conclude that recognition of these risk factors in patients with abdominal trauma should help clinicians to identify those at greatest risk for intraabdominal infection, in whom preventive measures, such as the administration of antibiotics and fluid resuscitation to avert hypotension, should be implemented early. -AT


Morales CH, et al. Arch Surg 2004;139(12): 1278-85.



Ultrasonography enhances the activity of tissue plasminogen activator.

A recent study has revealed that patients who receive continuous transcranial Doppler ultrasonography concomitantly with tissue plasminogen activator (tPA) for acute ischemic stroke achieve both more complete arterial recanalization, because of the thrombolysis-enhancing effects of the technology, and a possibly greater degree of clinical recovery, compared with patients who don't receive it.


In a multicenter, phase 2 clinical trial, the Combined Lysis of Thrombus in Brain Ischemia Using Transcranial Ultrasound and Systemic tPA (CLOTBUST) study, 126 patients with acute ischemic stroke were randomly assigned to receive either tPA therapy with continuous 2-MHz transcranial Doppler ultrasonography (n = 63) or tPA with placebo monitoring (n = 63) within three hours of the insult. Eligibility criteria included obstructive residual blood flow in the middle cerebral artery with a flow grade of 0 to 3 on the Thrombolysis in Brain Ischemia scale, on which grade 5 represents complete recanalization. After tPA bolus administration, ultrasonographic monitoring was conducted for two hours, with measurements taken at 30, 60, 90, and 120 minutes. Neurologic status also was assessed at the same points in time, as well as at 24 hours, using the National Institutes of Health Stroke Scale, and at three months with modified Rankin scores. The primary end point was complete arterial recanalization or early or significant clinical recovery--the incidence of intracerebral hemorrhage with deterioration of clinical status was the primary safety end point.


Forty-nine percent of the patients in the intervention group achieved the primary end point, compared with 30% in the control group, within 120 minutes of tPA bolus administration. More specifically, complete recanalization occurred in 46% of patients in the intervention group, compared with 18% in the control group, and the effects were sustained in the former group in a significantly greater proportion, as well. Symptomatic intracerebral hemorrhage occurred in 4.8% of the patients in each group. During the follow-up period (in which assessments were done at 24 hours and at three months), a greater proportion of patients in the intervention group demonstrated significant clinical recovery and better outcomes, compared with those in the control group, although those results didn't reach statistical significance.-JC


Alexandrov AV, et al. N Engl J Med 2004; 351(21):2170-8.



Mortality rate higher when adherence to treatment guidelines is poorer.

Early invasive management in the high-risk patient with a non-ST-segment elevation acute coronary syndrome (NSTE ACS) is underused, according to results of the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines quality improvement initiative. Poor adherence to the American College of Cardiology-American Heart Association (ACC-AHA) guidelines regarding early invasive management of an NSTE ACS was associated with a higher mortality rate in the hospital, according to the results of the observational, retrospective review.


Data in the medical records of 17,926 patients with a high-risk NSTE ACS who presented within 48 hours of having ischemic symptoms at rest at 248 U.S. hospitals having cardiac catheterization and percutaneous coronary intervention or coronary artery bypass grafting facilities were analyzed for an association between early invasive management (within 24 hours of presentation) and death in the hospital. High-risk factors found in the data were ST-segment depression, transient ST-segment elevation, and positive cardiac markers (elevated troponin I or T or creatine kinase-MB levels, or both). Only 44.8% of patients at high risk received early invasive management, 75% of them undergoing revascularization. Adjusted rates of mortality in the hospital were significantly lower among the patients who received early invasive management-2.5% compared with 3.7%, and there were also a lower risk of myocardial infarction and shorter lengths of hospital stay in that group.


The strongest predictor of early invasive management was cardiology care, followed by younger age. Patients who were older and had more comorbidities tended to receive conservative medical management, despite evidence from clinical trials indicating that such patients benefit from the more aggressive treatment strategy.


Limitations of the study include its retrospective, nonrandomized design and the inability to adjust for possible unknown confounding variables. Also, voluntary participation in the initiative may have skewed the sample to a population of patients treated in facilities concerned with improving the quality of care and adherence to treatment guidelines-mortality rates may be higher in other hospitals and in those that do not have facilities for cardiac catheterization.-FM


Bhatt DL, et al. JAMA 2004;292(17):2096-104.



The former may be more effective.

In patients presenting within six hours of the onset of focal stroke symptoms, magnetic resonance imaging (MRI) that includes diffusion-weight imaging and gradient recalled echo (GRE) detects acute cerebral hemorrhage as well as noncontrast computed tomography (CT), and detects hemorrhagic transformation of acute ischemia and chronic blood, including micro-bleeds, better than noncontrast CT, according to results of the Hemorrhage and Early MRI Evaluation study.


In the prospective comparison study, readers (two neuroradiologists and two stroke neurologists) who were blinded to the patients' final discharge diagnoses interpreted MRI and computed tomographic images obtained in the hyperacute phase of stroke (zero to six hours). Hemorrhage was detected in 129 patients; only one case was not seen on MRI, but four acute and 52 chronic hemorrhages were missed on CT. All intraparenchymal hematomas were detected with MRI with GRE, but in three cases they were interpreted as chronic instead of acute. Most of the chronic hemorrhages were microbleeds, which may represent a risk factor for hemorrhage if thrombolytic therapy is given. MRI was found to be superior in detecting hemorrhagic transformation of ischemic areas, and while CT was superior in determining whether small hemorrhages were acute or chronic, MRI was as effective in detecting them.


The study demonstrates the efficacy of MRI in detecting intracerebral hemorrhage. At stroke centers at which there is much expertise in the interpretation of MRI, it might be considered as the only neuroimaging study to use for the evaluation of acute stroke.-FM


Kidwell CS, et al. JAMA 2004;292(15): 1823-30.



It may often have adverse outcomes.

The risk of death is higher when patients with acute coronary syndromes receive blood transfusions for anemia that develops during hospitalization, according to the results of a post hoc analysis of clinical trials data.


Because an increasing number of patients with heart disease undergo invasive procedures or receive antithrombotic or fibrinolytic drugs, or both, the risk of the development of bleeding and anemia after admission also is increasing. Because it is not known whether blood transfusion is beneficial in these circumstances, researchers analyzed data collected in three large international clinical trials that had enrolled 24,112 patients with acute coronary sydromes--10% (2401) were found to have had transfusions of "packed" red blood cells or whole blood. Rates of 30-day death from all causes, of myocardial infarction (MI), and of the composite of 30-day death or MI among patients who had received transfusions were compared with those of patients who had not. The unadjusted rate of each was significantly greater in patients who had received a transfusion, and after adjusting for demographic characteristics, invasive procedures, and bleeding, the hazard ratio for death was 3.94. However, when data were adjusted for the degree of anemia that developed after admission, as determined by a lowest postadmission hematocrit greater than or less than 25%, a greater risk of death associated with transfusion was found only in patients with the lower hematocrit.


The evidence indicating that blood transfusion increases tissue oxygenation is inconclusive. The authors speculate that chemical changes that red blood cells undergo when stored could decrease their ability to bring oxygen to tissues, including the myocardium, and other studies do not provide clear evidence that transfusion benefits coronary disease patients who develop anemia but whose hematocrit does not fall below 25% after hospitalization.


Because of the disparity between this study's results and those of other observational studies, the authors assert that a randomized trial is warranted and advise the exercise of caution in regard to the routine use of blood transfusion in patients with ischemic heart disease.-FM


Rao SV, et al. JAMA 2004;292(13):1555-62.