Required Rescue Therapy Research Articles

Glucomannan for abdominal pain-related functional gastrointestinal disorders in children: a randomized trial.

To assess the efficacy of glucomannan (GNN) as the sole treatment for abdominal pain-related functional gastrointestinal disorders (FGIDs). We conducted a double-blind, placebo-controlled, randomized trial. Patients were recruited among children referred to the Department of Paediatrics, Medical University of Warsaw. Included in the study were children aged 7-17 years with abdominal pain-related FGIDs classified according to the Rome III diagnostic criteria. The children were randomly assigned to receive GNN, a polysaccharide of 1,4-D-glucose and D-mannose, a soluble fiber from the Japanese Konjac plant, at a dosage of 2.52 g/d (1 sachet of 1.26 g 2 times a day), or a comparable placebo (maltodextrin) at the same dosage. The content of each sachet was dissolved in approximately 125 mL of fluid and was consumed twice daily for 4 wk. Of the 89 eligible children, 84 (94%) completed the study. "No pain" and "treatment success" (defined as no pain or a decrease ≥ 2/6 points on the FACES Pain Scale Revised) were similar in the GNN (n = 41) and placebo (n = 43) groups [no pain (12/41 vs 6/43, respectively; RR = 2.1, 95%CI: 0.87-5.07) as well as treatment success (23/41 vs 20/43; RR = 1.2, 95%CI: 0.79-1.83)]. No significant differences between the groups were observed in the secondary outcomes, such as abdominal cramps, abdominal bloating/gassiness, episodes of nausea or vomiting, or a changed in stool consistency. GNN demonstrated no significant influence on the number of children requiring rescue therapy, school absenteeism, or daily activities. In our setting, GNN, as dosed in this study, was no more effective than the placebo in achieving therapeutic success in the management of FGIDs in children.

Infliximab versus cyclosporine as rescue therapy in acute severe steroid-refractory ulcerative colitis: a systematic review and meta-analysis

Acute severe colitis affects 25 % of patients with ulcerative colitis (UC). Up to 30-40 % of these patients are resistant to intensive steroid therapy and therefore require rescue therapy to prevent emergent colectomy. Data comparing rescue therapy using infliximab and cyclosporine are limited and equivocal. This study evaluates the outcomes of UC patients receiving infliximab or cyclosporine as rescue therapy in acute severe steroid-refractory exacerbations. Electronic databases (PubMed, EMBASE, and Cochrane database) were searched for studies directly comparing infliximab and cyclosporine in UC, and references of included studies were screened. Two independent reviewers identified relevant studies and extracted data. Meta-analyses were performed using the random effect model. Outcome measures included 3- and 12-month colectomy rates, adverse drug reactions, and postoperative complications. Six retrospective cohort studies describing 321 patients met the inclusion criteria. The meta-analysis did not show significant differences between infliximab and cyclosporine in the 3-month colectomy rate (odds ratio (OR) = 0.86, 95 % confidence interval (CI) = 0.31-2.41, p = 0.775), in the 12-month colectomy rate (OR = 0.60, 95 % CI = 0.19-1.89, p = 0.381), in adverse drug reactions (OR = 0.76, 95 % CI = 0.34-1.70, p = 0.508), and in postoperative complications (OR = 1.66, 95 % CI = 0.26-10.50, p = 0.591). Funnel plot revealed no publication bias. Infliximab and cyclosporine are comparable when used as rescue therapy in acute severe steroid-refractory UC. Randomized trials are required to further evaluate these agents.

Chapter 13: Potentially (near) fatal asthma

Potentially (near) fatal asthma (PFA) defines a subset of patients with asthma who are at increased risk for death from their disease. The diagnosis of PFA should motivate treating physicians, health professionals, and patients to be more aggressive in the monitoring, treatment, and control of this high-risk type of asthma. A diagnosis of PFA is made when any one of the following are present: (1) history of endotracheal intubation from asthma, (2) acute respiratory acidosis (pH < 7.35) or respiratory failure from acute severe asthma, (3) two or more episodes of acute pneumothorax or pneumomediastinum from asthma, (4) two or more episodes of acute severe asthma despite the use of long-term oral corticosteroids and other antiasthma medications. There are two predominant phenotypes of near fatal exacerbations, the "subacute" exacerbation and the "hyperacute" exacerbation. The best way to "treat" acute severe asthma is 3-7 days before it occurs (i.e., at the onset of symptoms or change in respiratory function) and to optimize control of asthma by decreasing the number of symptomatic days and days/nights requiring rescue therapy and increasing baseline respiratory status in "poor perceivers." PFA is treated with a multifaceted approach; physicians should appreciate limitations of pharmacotherapy including combination inhaled corticosteroid/long-acting beta-agonist products as well as addressing nonadherence, psychiatric, and socioeconomic issues that complicate care.

A Respiratory Centre and Network Model for the Management of Severe Hypoxaemic Respiratory Failure

The development of specialist respiratory centres for the management of severe refractory hypoxaemic respiratory failure is advocated based largely on three premises: 1. High volume units have better outcomes than smaller volume units.1-4 2. The provision of extra-corporeal membrane oxygenation (ECMO) in the UK is limited and patients should be selected according to need. Those patients requiring ECMO are best recognised by intensivists working in high volume centres, either following discussion with the smaller unit or following a trial of care in the high volume centre.5 3. Only larger units have what Bob Winter refers to in his editorial in the January 2011 issue of JICS as a ‘wider range of witchcraft’6 and others may know as high frequency oscillation (HFOV), and nitric oxide (NO). These may have a role as rescue therapies before a trial of ECMO. Those arguing against such logic point to the following flaws: 1. Comparing outcome of high volume to low volume units does not equate to the introduction of a policy to transfer patients failing conventional treatment. 2. Transfer of patients is already historically contentious7,8 and a second transfer for ECMO, following an initial transfer from a small unit to a respiratory centre is even more so. 3. There is a lack of compelling evidence demonstrating benefit from ECMO, HFOV, NO, and prone ventilation. To summarise, those arguing against the respiratory centre concept point to a lack of good evidence for its implementation, and worry that the real agenda is one of centralisation of services. Those arguing for respiratory centres cite the unintended consequence in the CESAR study, demonstrating that patients transferred but not receiving ECMO had better than expected outcomes.9 The document ‘The management of severe refractory hypoxia in critical care in the UK in 2010,’5 recommends that Networks implement the policy of identifying respiratory centres. In South East Wales we have had a managed clinical network for five years (SEWCCN), covering three of the seven recently created Welsh Health Boards (Aneurin Bevan, Cwm Taf and Cardiff and Vale University Health Board). Within the three Health Boards, there are five District General Hospital (DGH) critical care units which each have between 5-8 level 3 beds, and one Teaching Hospital Unit – University Hospital of Wales (UHW) – which has 14 level 3 beds (Table 1). Early in the 2009 H1N1 influenza A pandemic, it became clear that the morbidly obese and those with chronic lung disease were at greater risk of severe respiratory failure. South East Wales, with a population of 1.4 million, has a particularly high incidence of obesity10 and chronic lung disease11 related to previous industrial lung exposure, severe chronic social deprivation, and a high prevalence of cigarette smoking. We therefore expected to be particularly vulnerable to this pandemic, and set up in 2009 what would now be recognised as a ‘Respiratory Centre’ model. A series of meetings about influenza were organised by the Network to agree a way forward based on the information about H1N1 available at that time. When it became clear that ventilators planned for use to create surge capacity were not fit for the purpose of ventilating patients with severe refractory respiratory failure, the first step the Network took was to improve equipment in all units. Following discussion with the SEWCCN, the Welsh Assembly Government agreed to fund 50% of the level 3 surge capacity ventilators as intensive care unit ventilators. The second step, based upon the published experience particularly from North America and Australasia, was to develop local protocols: in Canada,12 81% of patients (n=168) were ventilated on the first day of critical care admission. Of those that required rescue therapy for hypoxia, 28% received neuromuscular blockade, 13.7% inhaled NO, 11.9% HFOV, 4.2% ECMO, and 3% prone ventilation. In Australasia 11.6% of those mechanically ventilated (n=456) received ECMO for H1N1 Hospital Number of Surge capacity Level 3 beds identified

Gemcitabine and Vinorelbine Therapy for Patients with Hodgkin Lymphoma

Hodgkin lymphoma (HL) is very responsive to front-line therapy, with durable event-free survival exceeding 75%. Survivors suffer long-term effects of therapy and some experience recurrent or refractory disease requiring rescue therapy. High-dose chemotherapy with autologous stem-cell transplantation increases the chance for long-term survival in this population, especially when reinduction therapy achieves complete response. As single agents, or within combination regimens, gemcitabine and vinorelbine have favorable toxicity profiles and are active against multiple malignancies, including relapsed and refractory HL. In Phase II trials the response to the combination of gemcitabine and vinorelbine in relapsed/refractory HL is better than or comparable to other more toxic regimens. The combination was not more effective than other drugs in front-line HL treatment; however, its addition to upfront therapy of slow-responding patients with HL is likely to enhance effectiveness with low toxicity.

Early worsening heart failure in patients admitted with acute heart failure – a new outcome measure associated with long‐term prognosis?

A major limitation in acute heart failure (AHF) research has been the lack of an outcome measure paralleling re-infarction in acute coronary syndromes. The aim of the present study was to assess the time course, prognostic factors and outcome of early worsening heart failure (WHF) in patients admitted for AHF to a community hospital. All AHF admissions between December 2003 and March 2004 in a regional medical center were recorded. Patients were followed through admission and for 6 months after discharge. Early WHF was defined as WHF occurring during the initial 7 days from admission. Study endpoints were cardiovascular mortality and WHF (defined as worsening or persistent signs or symptoms of AHF requiring rescue therapy or hospital readmission). Early WHF rate was 29% and was associated with markers of AHF severity on presentation (higher troponin I, lower oxygen saturation, need for mechanical ventilation, intravascular diuretics and inotropes). Early WHF was a powerful predictor of death during 6 months of follow up, with an age-adjusted hazard ratio of 3.3 (95% confidence interval 1.7-6.3). Early WHF is a common adverse event in patients admitted with AHF, and is associated with AHF severity and excessive 6-month mortality. WHF should be considered as a clinically important endpoint in AHF studies.

Review of inhaled iloprost for the control of pulmonary artery hypertension in children

In the pediatric population, pulmonary hypertension may present as an acute event in the setting of lung or cardiac pathology or as a chronic disease, mainly as idiopathic pulmonary hypertension or associated with congenital heart disease. Recently, new pharmacologic approaches have demonstrated significant efficacy in the management of adults with pulmonary arterial hypertension; these include intravenous epoprostenol, prostacyclin analogs, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors. The same treatment strategies are currently used in children. There are only few reports of the use of inhaled iloprost in pediatrics, only one of which reported the use of chronic inhaled iloprost in a significant number of children. This report showed that 1) the acute pulmonary vasodilator response to inhaled iloprost is equivalent to that of inhaled nitric oxide; 2) acute inhalation of iloprost can induce bronchoconstriction 3) the addition of inhaled iloprost can reduce the need for intravenous prostanoid therapy in some patients; 4) most children tolerated the combination of inhaled iloprost and endothelin receptor antagonist or phosphodiesterase inhibitors; 5) Several patients had clinical deterioration during chronic inhaled iloprost therapy and required rescue therapy with intravenous prostanoids. In this review we will discuss the role of inhaled iloprost in acute and chronic pulmonary hypertension in children.

A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Comparative Trial of AMD3100 (Plerixafor)+G-CSF vs. G-CSF+Placebo for Mobilization in Multiple Myeloma (MM) Patients for Autologous Hematopoietic Stem Cell (aHSC) Transplantation.

AMD3100, Plerixafor (A)+G-CSF (G) have effectively allowed aHSC mobilization in Phase I and II studies. This Phase III, multicenter, randomized, double-blind, placebo controlled study compares the safety and efficacy of A+G Vs. placebo (P)+G to mobilize and transplant patients with MM.Methods: Adult MM patients requiring an aHSC transplant, in first or second CR or PR were eligible to participate. Patients were declared for single or tandem transplant with the second transplant occurring within 6 months from the first. Patients received G (10μg/kg/day) subcutaneously (SQ) for 4 days; on the evening of Day 4 they received either A (240μg/kg SQ) or P. Patients underwent apheresis on Day 5 after an AM dose of G and 10–11 hours after administration of study treatment. Patients continued to receive the evening dose of study treatment followed by AM dose of G and apheresis for up to a total of 4 apheresis or until ≥6 x 106 CD34+ cells/kg were collected. Patients who failed to collect ≥2 x 106 CD34+ cells/kg were eligible for rescue therapy with A+G, without unblinding of randomized treatment. Only study cells were used for transplant. The primary endpoint was the percentage of patients who achieved ≥6 x 106 CD34+ cells/kg in 2 or less apheresis days. All patients will be followed for ≥12 months post-transplant.Results: 302 patients were enrolled and randomized into the study. All have completed 100 days follow-up and are included in this intent-to-treat analysis. Baseline characteristics were similar between groups. The primary endpoint was met in 106/128 (72%) patients in the A+G group and 53/154 (34%) patients in the P+G group, p<0.0001.The figure shows that 54% of A+G patients reached target after 1 day of apheresis but 56% P+G patients required up to 4 days of apheresis to reach target. 7 patients in the P+G group required rescue therapy and all collected ≥2 x 106 CD34+ cells/kg after A+G rescue. 142 patients (96%) in A+G group and 136 patients (88%) in the P+G group underwent transplant. Tandem transplants were performed in 32 and 28 patients in A+G and P+G groups, respectively. Median time to engraftment was Day 11 for PMN and Day 18 for platelets in both groups. Grafts were durable in all patients in both group at ≥100 days post-transplant. Patients in the A+G group experienced more GI effects and injection site erythema than patients in the P+G group. These adverse events were generally mild. There were no drug related serious adverse events in either group.Conclusions: In this study, the addition of AMD3100 to G-CSF is generally safe and well tolerated and is superior to G-CSF alone for aHSC mobilization in MM patients. A+G patients were statistically significantly more likely to achieve target earlier than P+G patients and had successful transplant. [Display omitted]

Selective surfactant prophylaxis in preterm infants born at ≤31 weeks' gestation using the stable microbubble test in gastric aspirates

To evaluate the stable microbubble test (SMT) ability to select candidates for surfactant prophylaxis for respiratory distress syndrome (RDS). We followed patients treated according to a new routine for surfactant prophylaxis based on the SMT to determine timing of the initial dose of surfactant, proportion of infants using surfactant, and the predictive value of the SMT. Gastric secretions were collected after birth. Newborns with < 25 microbubbles (MB)/mm(2) received prophylactic surfactant. Surfactant was given only after confirmation of RDS (rescue therapy) to newborns with > or =25 MB/mm(2). Fifty-four (55%) had a low MB count and received prophylactic surfactant. Three out of 44 infants with a high MB count required rescue therapy (negative predictive value 93%; CI:81.3-98.6%). The median interval and interquartile range between surfactant administration and birth in the prophylaxis group was 20 (17-27) minutes. Surfactant was used in 23 of 28 (82%) infants born at < 28 weeks of gestation and in 34 of 70 (49%) infants between 28 and 31 weeks. The SMT may be useful to determine surfactant prophylaxis (< 30 min after birth). This approach may reduce costs and the number of unnecessary interventions.

Individualized outcome feedback produces voluntary antiemetic prescribing practice changes

Study Objective: To determine the impact of individualized outcome feedback on antiemetic prescribing practices and compare outcomes of a cost-effective, standardized antiemetic protocol (PROT) to that of customized antiemetic therapy (NONPROT). Design: Prospective, observational study with randomized component. Setting: Postanesthesia care unit (PACU) of an academic medical center. Patients: 3027 consecutive ASA physical status I, II, and III patients receiving general anesthesia. Interventions: Patients were randomized to receive 0.625 mg droperidol or 4 mg ondansetron for postoperative nausea and/or vomiting (PONV) from a protocol, or received customized antiemetic therapy. Measurements and Main Results: Incidence of PACU PONV, selection of PROT versus NONPROT, patient satisfaction, and use of PONV prophylaxis were measured and indexed by an attending anesthesiologist in a monthly report for 4 months. Monthly expenditures for antiemetic therapy prior to, during, and after the study were collected. Literature on PONV outcomes, appropriate timing, and selection of PONV prophylaxis was distributed. The NONPROT group was slightly older than the PROT group; otherwise, demographics were similar between all groups. The incidence of PONV did not differ between the PROT and NONPROT groups (11% vs. 10%), and the incidence of PONV in patients receiving prophylaxis was higher in both groups (17% PROT vs. 15% NONPROT). Patients receiving ondansetron as a first-line drug required rescue therapy less often (5%) than those receiving droperidol (14%); however, patient satisfaction was indistinguishable among all groups. During the study, the use of prophylaxis decreased 47% without an increase in PONV, and PROT selection increased 54%. Conclusions: Individualized outcome feedback produced a 48% reduction in monthly expenditures for ondansetron and droperidol, which was sustained after the study. Patients satisfaction between ondansetron 4 mg and droperidol 0.625 mg given in the PACU did not differ in spite of a slightly greater efficacy of ondansetron as a first-line drug.

Montelukast, a Leukotriene-Receptor Antagonist, for the Treatment of Mild Asthma and Exercise-Induced Bronchoconstriction

Patients with mild asthma frequently have only exercise-induced bronchoconstriction, a symptom of inadequate control of asthma. We evaluated the ability of montelukast, a leukotriene-receptor antagonist, to protect such patients against exercise-induced bronchoconstriction. We randomly assigned 110 patients (age, 15 to 45 years) with mild asthma and a decrease in the forced expiratory volume in one second (FEV1) of at least 20 percent after exercise on two occasions during a placebo run-in period to receive 10 mg of montelukast (54 patients) or placebo (56 patients) once daily at bedtime for 12 weeks in a double-blind study. Treatment was followed by a two-week, single-blind washout period during which all patients received placebo. Exercise challenges were performed at base line; 20 to 24 hours after dosing at weeks 4, 8, and 12; and at the end of the washout period. The primary end point was the area under the curve for FEV1 (expressed as the percent change from base-line values) in the first 60 minutes after exercise. This measure summarized the extent and duration of bronchoconstriction after exercise. At 12 weeks, montelukast therapy offered significantly greater protection against exercise-induced bronchoconstriction than placebo therapy (expressed as the percentage of inhibition of the end points), as evidenced by the improvement in the area under the FEV1 curve (degree of inhibition, 47.4 percent; P=0.002). Montelukast therapy was also associated with a significant improvement in the maximal decrease in FEV1 after exercise (P=0.003) and the time from the maximal decrease in FEV1 to the return of lung function to within 5 percent of pre-exercise values (P=0.04). The differences between groups in the various measures of lung function were similar at 4, 8, and 12 weeks; there was no evidence of rebound worsening of lung function in the montelukast group after the washout period. After 12 weeks of treatment, patients in the montelukast group were more likely to rate their asthma control as better and less likely to require rescue therapy with a beta-agonist during or after exercise challenge. The rates of adverse events were similar in the two groups. As compared with placebo, once-daily treatment with montelukast provided significant protection against exercise-induced asthma over a 12-week period. Tolerance to the medication and rebound worsening of lung function after discontinuation of treatment were not seen.

Formoterol in the Treatment of Nocturnal Asthma

Formoterol fumarate is a new beta 2-adrenergic agonist with a long lasting effect. The bronchospasmolytic effect of 12 micrograms of formoterol was compared with that of 200 micrograms of albuterol (salbutamol) in a single-center, double-blind, randomized within-patient study. The drugs were given as aerosols by MDI to 16 patients with nocturnal asthma in a stable phase. The inhalations were given at 10 PM and the FEV1 values as parameter were measured before and at 1, 2, 6, 8, 10, and 12 hours afterwards. The FEV1 6 hours after administration of formoterol was significantly higher than that after albuterol (ANCOVA: p = 0.008), and this was still the case 12 hours after the test dose at 10 AM the following morning (ANCOVA: p = 0.009). At 4 AM, the FEV1 fell below the basic starting value after albuterol, whereas it remained at least 10 percent above the formoterol inhalation. Five patients required rescue therapy after albuterol and two after formoterol. We conclude that formoterol in a dose of 12 micrograms via MDI confers good protection against nocturnal asthma; this was only insufficient for some patients with severe asthma, and further studies with higher dosages in these patients are clearly indicated.