Prophylactic Use Of Dexamethasone Research Articles

Real-world experience with clinical management of talquetamab in relapsed/refractory multiple myeloma: a qualitative study of US healthcare providers

Objective Talquetamab is the first-in-class GPRC5DxCD3 bispecific antibody for relapsed/refractory multiple myeloma. Given limited real-world data, this study was conducted with US healthcare providers (HCPs) to understand real-world talquetamab dosing and symptom management. Methods In February/March 2024, individual in-depth interviews (IDIs; n = 10) were conducted with HCPs administering talquetamab in real-world settings. A subsequent expert panel (n = 6) further discussed current practices. Results The IDIs reported a variety of settings for step-up dosing (SUD), including inpatient (n = 5), outpatient (n = 3), and hybrid models (n = 2), with a trend toward shorter SUD length to reduce healthcare resource utilization. Most HCPs used a biweekly (Q2W) schedule in SUD (n = 7) and treatment phases (n = 8). Six participants explored reducing dose frequency to every 4 weeks (Q4W) in patients following positive disease response to treatment, considering patient convenience and relieving GPRC5D-related symptoms. Panelists recommended symptom management and prophylactic strategies, such as dexamethasone and nystatin mouthwash or zinc and vitamin B complex for oral symptoms, and topical steroids and cosmetic products for skin and nail symptoms. Conclusion This study outlines current real-world practices for talquetamab. Findings indicate variation in the SUD care setting. The 0.8 mg/kg Q2W dosing schedule was most common, although switching to Q4W is a real-world symptom management strategy for some patients with responses to therapy. GPRC5D-related symptom management approaches are evolving; prophylactic use of dexamethasone and nystatin mouthwash or zinc and vitamin B complex may be effective strategies to alleviate oral symptoms. Further real-world evidence is needed to inform optimal dosing schedules while mitigating symptom impact.

Abstract CT051: Preliminary results from LuCa-MERIT-1, a first-in-human Phase I trial evaluating the fixed antigen mRNA vaccine BNT116 + docetaxel in patients with advanced non-small cell lung cancer

Abstract Background: Non-small cell lung cancer (NSCLC) is often diagnosed late with many patients (pts) not responding to first line therapy or only responding for a limited time. BNT116 is an intravenously administered uridine RNA-based lipoplex cancer vaccine comprising six mRNAs (MAGE A3, CLDN6, KK-LC-1, PRAME, MAGE A4, MAGE C1), each encoding a tumor-associated antigen (TAA) frequently expressed in NSCLC. Here, we present preliminary results from pts with advanced unresectable or metastatic NSCLC (ECOG 0-1) receiving BNT116 + docetaxel (DTX). Methods: LuCa-MERIT-1 (NCT: 05142189, EudraCT: 2021-004739-94) is a first-in-human, open label, Phase I trial to determine safety (dose limiting toxicities [DLTs]; treatment-emergent adverse events [TEAEs]) and clinical activity (RECIST v1.1) of BNT116 alone or in combinations. The cohort reported here will inform the dose of BNT116 in combination with DTX. Pts must have progressed on PD-1/PD-L1 inhibitor and a platinum-based chemotherapy. Biomarker analysis includes e.g., immunogenicity (ELISpot, n=3), cytokines (MSD, n=20), ctDNA (Avenio ctDNA Surveillance, n=~20), and PD-L1 (IHC, n=20). Results: As of 01 DEC 2023, 20 pts (median age 66 years) have received BNT116 in addition to DTX at 75 mg/m2 Q3W. The combination demonstrated a manageable safety profile. All pts experienced at least one TEAE. TEAEs ≥Grade 3/4, (incidence rate ≥10%) include neutropenia (n=10 [50%]), pneumonia (n=3 [15%]), hypertension (n=3 [15%]), lymphocyte count decreased, diarrhea, and fatigue (each n=2 [10%]). Serious TEAEs were observed in ten pts (50%), of which three were considered as related to BNT116 (Grade 3 cytokine release syndrome, Grade 3 bronchospasm, and Grade 3 pyrexia) and three were considered as related to DTX (Grade 3 diarrhea, Grade 3 rash, and Grade 4 febrile neutropenia). No DLTs within the dose confirmation period or deaths under treatment were observed. Seven of 20 pts (35%) had a partial response, 10 of 20 pts (50%) had stable disease. The objective response rate was 35% (95% CI: 15.4-59.2) and the disease control rate was 85% (95% CI: 62.1-96.8). Robust antigen-specific T-cell responses and cytokine induction were observed even with the addition of DTX and the use of prophylactic dexamethasone on Day 2 of each cycle. Conclusions: BNT116 + DTX shows encouraging antitumor activity, consistent induction of immune responses, a manageable safety profile, and no signs of additive toxicity. Updated safety and clinical activity data will be presented along with additional biomarker data. (Funded by BioNTech) Citation Format: Bala Başak Öven, David Vicente Baz, Jürgen Wolf, Ozturk Ates, Erdem Göker, Patrick Brück, Michael Wenger, Neru Munshi, Iryna Tsyhankova, Iryna Tsyhankova, Malgorzata Kaczorowska, Thomas Schell, Janet L. Markman, Huyuan Yang, Özlem Türeci, Uğur Şahin, Patrick Forde, Akin Atmaca. Preliminary results from LuCa-MERIT-1, a first-in-human Phase I trial evaluating the fixed antigen mRNA vaccine BNT116 + docetaxel in patients with advanced non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT051.

Impact of prophylactic dexamethasone on the efficacy of immune checkpoint inhibitors plus platinum-based chemotherapy in patients with advanced Non-Squamous Non-Small-Cell lung cancer

BackgroundBaseline corticosteroids exposure is associated with inferior clinical outcomes in patients with non-small-cell lung cancer (NSCLC) treated with programmed cell death-1 (PD-1) axis blockade. Dexamethasone is a potent corticosteroid used in the prevention of chemotherapy-associated adverse events (CAAEs). ObjectiveSince dexamethasone has immunosuppressive properties, this study attempted to elucidate its effects on the efficacy of immunotherapy plus chemotherapy in patients with non-squamous NSCLC. MethodsThe study retrospectively analyzed the medical records of 254 advanced non-squamous NSCLC patients who received front-line treatment with a PD-1 pathway inhibitor and platinum-based chemotherapy at three academic institutions. The average dosage of prophylactic dexamethasone per chemotherapy cycle was calculated. Patients were divided into three groups based on the dose of dexamethasone: High-d (≥24 mg), Moderate-d (12–24 mg), and Low-d (<12 mg). Spearman's rank correlation was used to assess the correlation between the dosage of dexamethasone and progression-free survival (PFS). Logistic regression was used to assess the correlation between dexamethasone dosage and the occurrence of immune related adverse effects (irAE). Univariate and multivariate Cox proportional hazards regression models were used to analyze the differences in survival among the different dexamethasone dosage groups. ResultThe dosage of prophylactic dexamethasone was not significantly correlated with PFS (Spearman’s rho = -0.103, P = 0.098). Results from the univariate [hazard ratio (HR)Low-d/High-d, 1.00; P = 0.997; HRModerate-d/High-d, 0.85; P = 0.438] and multivariate (HRLow-d/High-d, 0.71; P = 0.174; HRModerate-d/High-d, 0.87; P = 0.512) analyses showed no significant association between dexamethasone and PFS. Dexamethasone did not have significant effect on the objective response rate, disease control rate or overall survival. The toxicity profiles of irAE were similar across all three groups. ConclusionThe results of this study suggest that the use of prophylactic dexamethasone does not have an adverse effect on the clinical outcomes of non-squamous NSCLC patients treated with PD-1 blockade therapy and chemotherapy. Routine use of dexamethasone for preventing CAAEs should be recommended for patients undergoing combined immunotherapy and chemotherapy.

Baseline CRP and Ferritin Identify Patients at High Risk of Poor Outcomes after Axicabtagene Ciloleucel Despite Corticosteroid Prophylaxis

Introduction: We and others have reported the role of cytokines and the tumor microenvironment on the development of severe grade >3 toxicities and CAR T resistance in recipients of CD19 targeted therapy. However, these analyses are not readily available outside of research settings. Early intervention and prophylactic strategies with cytokine blocking agents and/or steroids to mitigate severe toxicity have been explored. In a recent analysis of cohort 6 of the ZUMA-1 trial, investigators reported improved rates of severe toxicity with the prophylactic use of dexamethasone (Oluwole OO, Br J Haematol 2021). There is limited data on which patients benefit the most from such strategies. Methods: This is a study to evaluate factors associated with the development of severe immune mediated toxicities and treatment resistance in patients with R/R DLBCL treated with standard of care axicabtagene ciloleucel (axi-cel) at Moffitt Cancer Center. Baseline samples of CRP, LDH and ferritin were collected within one week prior to lymphodepleting chemotherapy. Cytokine analyses were performed as previously described (Faramand R, CCR 2020). Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded based on ASTCT criteria. Patients were stratified into three risk groups based on baseline CRP and ferritin; low risk (CRP <4gm/dL and ferritin <400ng/dL), intermediate (not meeting criteria for high risk or low risk), and high risk (CRP >4gm/dL and ferritin >400ng/dL). During the study period, institutional clinical standards were revised to administer prophylactic corticosteroids consecutively to all patients meeting high risk criteria. Patient survival outcomes were compared using Kaplan-Meier curves and subsequent log-rank tests. Multivariable Cox proportional hazards regression model with adjustment for clinical covariates was used to estimate hazard ratios for survival outcomes. Results: 136 patients with R/R DLBCL treated with axi-cel (>2 lines of therapy) are included in this study. Baseline patient characteristics and outcomes are summarized in Table 1. Most patients developed CRS (n=126) with 10.3% developing severe (gr. >3) CRS. Eighty-three patients (61%) developed ICANS with 28% having severe gr. >3 toxicity. The median overall survival (OS) was 34.9 months with a median progression free survival (PFS) of 12.2 months. We previously reported association of baseline elevated IL6 levels with poor clinical outcomes. Baseline IL6 levels correlated (p<0.0001, Fig. 1A) with risk category based on CRP and ferritin. Rates of severe CRS (25.9 vs. 1.61%, p=0.001) and ICANS ( 51.9 vs. 16.1%, p=0.002) were significantly higher in the high-risk (HR) group in comparison to the low risk group. Median PFS was 3 months, 7.9 and not reached in the high, intermediate and low risk groups respectively (p=0.0001) (Fig. 1B). The median OS was significantly inferior in the HR group at 6.9 months compared to 14.9 months and not reached in the intermediate and low groups respectively (p<0.0001) (Fig. 1C). Based on the above risk stratification, ten additional patients met HR criteria and were treated with prophylactic dexamethasone for three days starting on the day of CAR T cell infusion. Although most patients (90%) developed CRS, none developed severe CRS in the prophylactic steroids group which compares favorably to 25.9% observed in historical HR patients who did not receive prophylactic steroids (p=0.16). Severe ICANS was lower (30%) in the prophylactic cohort as compared to 52% in historical HR patients (p=0.29). The median PFS and OS were 2.9 and 5.9 months respectively in recipients of prophylactic steroids. Discussion: We establish that baseline elevated levels of CRP and Ferritin are associated with severe toxicity, and significantly inferior PFS and OS. Patients in the low risk group have excellent outcomes in terms of toxicity and efficacy using standard treatment paradigms negating the need for steroid prophylaxis and may be considered for outpatient treatment. In this report, prophylactic steroids were only used in 10 patients meeting high risk criteria. While there were no cases of severe CRS, efficacy outcomes remained poor in this high-risk cohort despite steroid prophylaxis. High risk patients can be easily identified prior to treatment with CAR T using standard labs and are encouraged to enroll on clinical trials to improve outcomes. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

PO-1467 Prophylactic use of dexamethasone during cerebral irradiation: Survey in Germany

PO-1467 Prophylactic use of dexamethasone during cerebral irradiation: Survey in Germany

Abstract 2048: Discovery of induction and release of IL-1b are unique and on-target effects of GSPT1 degradation that provide potential mitigation strategies to hypotension in the CC-90009-AML-001 phase 1 trial

Abstract CC-90009 is a novel cereblon (CRBN) E3 ligase modulator (CELMoD) that has demonstrated antileukemic activity and is under investigation in the CC-90009-AML-001 phase I trial (NCT02848001) in patients with relapsed or refractory acute myeloid leukemia (AML). In preclinical studies, CC-90009 drives the binding of translation termination factor G1 to S phase transition I (GSPT1) to CRBN. This results in ubiquitination and proteasome-dependent degradation of GSPT1, leading to activation of the integrated stress response, inhibition of nonsense-mediated decay, and induction of apoptosis. Hypotension, contemporaneous with blast and white blood cell (WBC) decreases, has emerged as a dose-limiting toxicity (DLT) in this ongoing phase I trial. Based on clinical observations, CC-90009-induced cytokine release during leukemic cell death was investigated as a potential cause of hypotension. Using electrochemiluminescence, flow cytometry and western blots, CC-90009-induced IL-1b release was observed in AML cell lines and primary AML bone marrow mononuclear cells. Induction of IL-1b was typically observed after caspase 3 and 8 activation, suggesting a cell-death-related mechanism consistent with clinical findings of hypotension reported after rapid WBC loss. In vitro models showed compounds leading to GSPT1 degradation were more potent IL-1b inducers compared to compounds with other mechanisms, including standard-of-care agents for AML, other cytotoxic agents, protein translation inhibitors, and unfolded protein response inducers. IL-1b induction as a downstream result of GSPT1 degradation was further confirmed by cells expressing non-degradable GSPT1 mutant protein where compound treatment did not induce IL-1b. CC-90009 activates the GCN2 pathway, resulting in caspase-3 and -8-mediated apoptosis. Caspase 8 is known to directly process pro-IL-1b into mature IL-1b. Using an isogenic MV4-11 Cas9 cell pair with wild-type vs null GCN2 status, GCN2 activation downstream of GSPT1 degradation was shown to be required for pro-IL-1b upregulation and caspase 8 activation. Furthermore, genetic and pharmacologic suppression of caspase 8 revealed that its activity was necessary, but not sufficient, for IL-1b release by CC-90009. Of note, dexamethasone (DEX) dampened CC-90009-mediated IL-1b induction without altering the rate or depth of AML cell killing, providing a mechanism-based strategy to manage CC-90009-induced hypotension. The ongoing trial was amended to allow the use of prophylactic DEX; dose escalation is still ongoing, including dose levels higher than the non-tolerated dose defined prior to mandating the use of prophylactic DEX. The insights derived from this study have facilitated GSPT1 targeting in AML therapy by enabling the testing of higher drug exposures. Citation Format: Tsun-Wen Sheena Yao, Yumin Dai, Carla Guarinos, Manuel Sanchez, Alicia Benitez, Hongbin Wang, Soraya Carrancio, Tonia Buchholz, Gang Lu, Michael Pourdehnad, Daniel Pierce, Jinhong Fan. Discovery of induction and release of IL-1b are unique and on-target effects of GSPT1 degradation that provide potential mitigation strategies to hypotension in the CC-90009-AML-001 phase 1 trial [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2048.

Routine antiemetic prophylaxis with dexamethasone during COVID-19: Should oncologists reconsider?

The ongoing pandemic caused by severe acute respiratory syndrome (SARS) coronavirus type 2 (SARS-CoV-2, also known as COVID-19) has caused unprecedented strain on the global healthcare system, causing thousands of deaths worldwide. Patients with underlying conditions such as cancer are at substantial risk of acquiring and dying from this novel coronavirus. Numerous reports have shown that infection with SARS-CoV-2 causes depletion of B- and T-lymphocytes, including CD4 and CD8 T-cells, and is associated with severe illness and death and that patients with higher lymphocyte levels may have better outcomes. Dexamethasone, a widely prescribed antiemetic for acute and delayed nausea and vomiting from a variety of cancer drugs, causes B and T cell depletion, which may augment immunosuppression. Since it seems that lymphocytes are vital in the immune response to novel coronavirus, oncologists should reconsider the routine use of prophylactic dexamethasone in uninfected patients, to avoid inducing lymphopenia, which may increase risk of infection or lead to inferior outcomes if a cancer patient subsequently becomes infected. Since many cancer drugs and malignant diseases inherently cause lymphopenia, further reduction of lymphocytes with dexamethasone should be avoided if possible and if safe and effective alternative antiemetics are available during the COVID-19 crisis.

Comparison of Granisetron and Dexamethasone in management of post operative nausea and vomiting (PONV) in laparoscopic gynaecological surgery

Background: Postoperative nausea and vomiting (PONV) is a common problem. It is more common inlaparoscopic surgery than in open surgery and following laparoscopic gynaecological surgery. PONVcauses patient discomfort and can prolong the time of hospital discharge.It causes potential hospitalburden and loss of unanticipated working time both for the patients and doctors. Management of thisproblem based on prevention rather than treatment. Various antiemetic drugs including steroids areeffective in the prevention of PONV but which one is better still now a debateable one. On the basis of thisfact there were numerous research, articles, analysis and publication work done all over the world. Objectives: Comparison of granisetron and dexamethasone to detect which one is better in managementof PONV after laparoscopic surgery. Method: The patient were selected after ethical committee approval. After informed written consent wehave selected 100 ASA- I &amp; II patients undergoing general anaesthesia for laparoscopic gynaecologicalsurgery in a prospective double blind randomized study. Patients who had received opoids, NSAIDS,steroids or antiemetic agent before previous 4 weeks or who has known hypersensitivity to granisetron ordexamethasone. Patients were divided as group-A (granisetron) and Group-B(dexamethasone). 50 patientwere member of each group. Every patient got study drug during induction. Group-A got granisetron andgroup-B got dexamethasone for prevention of PONV. There were no differences in background factors orfactors related to anaesthesia, analgesics consumption, pain or side effects between groups. The data collectedin a fixed protocol form from the patient consented for the study. After collection of data were coded, edited,compiled and entered into computer system for analysis. The result will help to guide the anaesthesiologistspracticing in the third world countries like Bangladesh in the management of PONV. Results: The current study showed the intravenous injection of 8 mg dexamethasone, or 3 mg Granisetronhave similar effects on PONV prophylaxis in laparoscopic gynaecological surgery. These results of thecurrent study indicated that Dexamethasone is a suitable substitute for Granisetron. Conclusion: Dexamethasone and Granisetron are comparable in management of PONV. These drugsinjection before anesthesia induction have similar effects on nausea and vomiting prophylaxis afterlaparoscopic gynaecological surgery. Prophylactic use of dexamethasone should be routine to preventPONV because dexamethasone is cost effective than granisetron. JBSA 2020; 33(1): 36-42

Effects of dexamethasone on early cognitive decline after cardiac surgery: A randomised controlled trial.

Postoperative cognitive decline (POCD), a very common complication after cardiac surgery, is characterised by impairment of both memory function and intellectual ability as well as being associated with increased use of healthcare resources. The investigators focused on the role of the inflammatory response to a surgical procedure as a potential factor involved in the pathogenesis of POCD. The use of prophylactic dexamethasone to attenuate the inflammatory response was hypothesised to reduce the risk of POCD. Randomised controlled study. Single university teaching hospital, from March 2015 to January 2016. A total of 169 patients scheduled for elective cardiac surgery were enrolled, and 161 patients were included in the analyses. Patients were randomised to receive a single intravenous bolus of 0.1 mg kg dexamethasone (n = 85) or placebo (n = 84) 10 h before the surgery. The primary outcome measure in both groups was the incidence of POCD on the 6th day after surgery. The investigators also evaluated the effect of dexamethasone on the incidence of systemic inflammatory response syndrome, postoperative C-reactive protein levels and postoperative serum S100β protein levels. Compared to the placebo group, the dexamethasone group showed statistically significant reductions in the incidence of POCD (relative risk, 0.43; 95% confidence interval, 0.21 to 0.89; P = 0.02), the incidence of systemic inflammatory response syndrome (30.0 versus 58.0%, P < 0.001) and postoperative C-reactive protein levels (P < 0.001). Postoperative S100β levels were insignificantly lower (P = 0.56) in the dexamethasone group. Preoperative administration of dexamethasone reduced the inflammatory response and thereby decreased the risk of early POCD after cardiac surgery. Clinicaltrials.gov identifier: NCT02767713.

The prophylactic effect of dexamethasone on postoperative sore throat in prone position surgery.

BackgroundSore throat and hoarseness are common complications after general anesthesia with tracheal intubation. The position for patients can affect the incidence of postoperative sore throat (POST) by causing displacement of the endotracheal tube. This study investigated the prophylactic effect of dexamethasone in prone position surgeries.MethodsOne hundred-fifty patients undergoing lumbar spine surgery (18-75 yr) were randomly allocated into the normal saline group (group P, n = 50), dexamethasone 0.1 mg/kg group (group D1, n = 50) or dexamethasone 0.2 mg/kg group (group D2, n = 50). The incidence and severity of POST, hoarseness, and cough were measured using direct interview at 1, 6, and 24 h after tracheal extubation. The severity of POST, hoarseness, and cough were graded using a 4-point scale.ResultsAt 1, 6, and 24 h after extubation, the incidence of sore throat was significantly lower in group D1 (1 h; P = 0.015, 6 h; P < 0.001, 24 h; P = 0.038) and group D2 (1 h; P < 0.001, 6 h; P < 0.001, 24 h; P = 0.017) compared to group P. There were less number of patients in the groups D1 and D2 than group P suffering from moderate grade of POST at 1, 24 h after extubation. The incidence of hoarseness at 1, 6, and 24 h after extubation was significantly lower in groups D2 than group P (P < 0.001). There were no significant differences in the incidence of cough among the three groups.ConclusionsThe prophylactic use of dexamethasone 0.1 mg/kg and 0.2 mg/kg in prone surgery reduces the incidence of postoperative sore throat and dexamethasone 0.2 mg/kg decreases the incidence of hoarseness.

Postembolization Syndrome after Hepatic Transarterial Chemoembolization: Effect of Prophylactic Steroids on Postprocedure Medication Requirements

PurposeTo evaluate the impact of prophylactic use of dexamethasone and scopolamine on analgesic and antiemetic agent requirements after transarterial chemoembolization. Materials and MethodsA total of 148 patients underwent 316 rounds of chemoembolization for hepatocellular carcinoma at a single institution over a 17-month period. Patient charts were retrospectively reviewed for demographic data, procedural technique, and use of analgesic and antiemetic medications. Patients were grouped into three categories: group A received steroid prophylaxis before and after the procedure, group B received steroid prophylaxis before the procedure only, and group C received no steroid prophylaxis. ResultsAnalysis was performed on 125 patients undergoing 252 procedures. Demographics were similar among groups. Overall, 86 (68.8%) were male, and mean age was 62 years (range, 39–82 y). Ninety-one patients (75%) had Child–Pugh class A cirrhosis and 25% had Child–Pugh class B cirrhosis. Dexamethasone was not significantly associated with decreased analgesic agent use (P = .6). Group A patients used significantly fewer antiemetic agents (Δ = 0.89; P = .007) compared with group C. A transdermal scopolamine patch was not associated with reduced use of antiemetic agents (P = .3). Age was inversely associated with analgesic (P <.001) and antiemetic agent use (P = .004). Men received significantly fewer antiemetic agents than women (P = .002), whereas there was no significant difference in analgesic agent use (P = .7). ConclusionsThe use of steroids did not affect analgesic agent use and had a minor effect on antiemetic requirements. The use of a scopolamine patch was not associated with reduced antiemetic agent use.

Dexamethasone for Antiemesis in Laparoscopic Gynecologic Surgery

To estimate the beneficial and harmful effects of dexamethasone for prevention of postoperative nausea and vomiting in women undergoing laparoscopic gynecologic surgery. We searched the following bibliographic databases: MEDLINE (from 1946 to January 2012), Embase (from 1980 to 2012 week 3), the Cochrane Central Register of Controlled Trials (from inception to January 2012), and ISI Web of Knowledge (from 1950 to January 2012). We also screened trial registries, reference lists of retrieved studies, and other sources of unpublished literature. Two reviewers screened in duplicate and independently searched results for inclusion. We included randomized controlled trials (RCTs) comparing dexamethasone with a placebo in patients undergoing laparoscopic gynecologic surgery. Two reviewers completed data extraction and assessed trials for bias in duplicate and independently. We used the Grading of Recommendations Assessment, Development, and Evaluation methodology to assess the quality of evidence across studies at the outcome level. A total of 13 RCTs with 1,695 patients met inclusion criteria. Data were pooled based on the random-effects model. The use of prophylactic dexamethasone significantly decreases the incidence of postoperative nausea (relative risk [RR] 0.56, 95% confidence interval [CI] 0.45-0.71), postoperative vomiting (RR 0.35, 95% CI 0.25-0.48), the need for rescue antiemetics (RR 0.39, 95% CI 0.29-0.52), and time to meet discharge criteria (mean 28.5 minutes, 95% CI 24.6-32.4). The estimated number needed to treat to prevent nausea in one patient was eight (95% CI 5-13), whereas that for vomiting was five (95% CI 4-6). There was no observed increase in adverse events. The quality of the evidence ranged from very low to moderate. This systematic review provides evidence that dexamethasone decreases the incidence of postoperative nausea and vomiting after laparoscopic gynecologic surgery, with no observed increase in side effects.

Effects on blood glucose of prophylactic dexamethasone for postoperative nausea and vomiting in diabetics and non-diabetics

Postoperative nausea and vomiting (PONV) prophylaxis with dexamethasone may produce significant hyperglycemia in the postoperative period. To evaluate if this effect is of greater severity in type 2 diabetics compared with non-diabetic patients. Forty non-diabetic and thirty type 2 diabetic patients undergoing laparoscopic cholecystectomy were studied in a prospective and double-blind fashion manner. Patients were randomly distributed into 4 groups: Group I, non-diabetics control (n = 20), Group II, non-diabetics dexamethasone (n = 20), Group III, type 2 diabetics control (n = 15), and Group IV, type 2 diabetics dexamethasone (n = 15). Immediately after induction, patients in groups I and III received isotonic saline and patients in the dexamethasone groups received 8 mg i.v. of the steroid. Capillary blood glucose concentrations were measured at baseline and every 2 hours during the first 12 hours since the start of surgery. A linear mixed effect model, adjusted for baseline capillary glucose concentration, age and duration of surgery was used to analyze the data. No effect of the presence of diabetes mellitus was observed in the evolution of glucose concentrations. There was a difference in capillary glucose concentrations between patients who received dexamethasone and placebo that started 2 hours post-intervention, reaching a mean maximum difference of 34 mg/dl (adjusted model, p < 0.001) at 10 hours post-intervention. In this study, Type 2 diabetic patients did not show a higher susceptibility than non-diabetics to develop postoperative hyperglycemia after the use of prophylactic dexamethasone for PONV.

Dexametasona para profilaxis de náuseas y vómitos postoperatorios: efecto sobre la glicemia en pacientes con diabetes mellitus tipo 2 y en no diabéticos sometidos a cirugía laparoscópica

Postoperative nausea and vomiting (PONV) prophylaxis with dexamethasone may produce significant hyperglycemia in the postoperative period.To evaluate if this effect is of greater severity in type 2 diabetics compared with non-diabetic patients.Forty non-diabetic and thirty type 2 diabetic patients undergoing laparoscopic cholecystectomy were studied in a prospective and double-blind fashion manner. Patients were randomly distributed into 4 groups: Group I, non-diabetics control (n = 20), Group II, non-diabetics dexamethasone (n = 20), Group III, type 2 diabetics control (n = 15), and Group IV, type 2 diabetics dexamethasone (n = 15). Immediately after induction, patients in groups I and III received isotonic saline and patients in the dexamethasone groups received 8 mg i.v. of the steroid. Capillary blood glucose concentrations were measured at baseline and every 2 hours during the first 12 hours since the start of surgery. A linear mixed effect model, adjusted for baseline capillary glucose concentration, age and duration of surgery was used to analyze the data.No effect of the presence of diabetes mellitus was observed in the evolution of glucose concentrations. There was a difference in capillary glucose concentrations between patients who received dexamethasone and placebo that started 2 hours post-intervention, reaching a mean maximum difference of 34 mg/dl (adjusted model, p < 0.001) at 10 hours post-intervention.In this study, Type 2 diabetic patients did not show a higher susceptibility than non-diabetics to develop postoperative hyperglycemia after the use of prophylactic dexamethasone for PONV.

Sevoflurane with or without antiemetic prophylaxis of dexamethasone in spontaneously breathing patients undergoing outpatient anorectal surgery

Study Objective To evaluate the prophylactic use of dexamethasone with sevoflurane in outpatient anorectal surgery. Design Randomized, controlled study. Setting Operating room and Postanesthesia Care Unit of a general hospital. Patients 60 adult, ASA physical status I and II outpatients undergoing anorectal surgery. Interventions Patients were randomized to receive either dexamethasone 5 mg intravenously (IV; Group D; n = 30) or an equal volume of saline (Group S; n = 30) before anesthesia induction. Anesthesia was induced with propofol 2.5 mg.kg −1, fentanyl two μg.kg −1, and 2% lidocaine one mg.kg −1 followed by placement of a Laryngeal Mask Airway. Measurements Frequency of postoperative nausea and vomiting (PONV), visual analog scale (VAS) pain scores, and patient satisfaction were recorded. Main Results Frequency of PONV and VAS pain scores were significantly lower in Group D than Group S ( P < 0.05). The time required for “home readiness” was significantly shorter in Group D than Group S ( P < 0.05). Conclusions The prophylactic administration of 5 mg dexamethasone IV can reduce the frequency of PONV, lower VAS pain scores, facilitate recovery to home readiness, and improve satisfaction in outpatients undergoing anorectal surgery.

Does prophylactic use of dexamethasone have a role in reducing post extubation stridor and reintubation in children?

All children aged from 4 weeks to <5 year, were intubated for at least 48 hours [n=51] during 6 months. Data of the patients treated with DEX (0.5 ml/kg every 6 hours for 3 doses, beginning 6-12 hours prior to extubation) (n=30) were compared with control patients (who had not received medication) (n=21). The DEX and control groups were similar in age i.e., mean ages of DEX group were 16.85+/-14 months, and that of control group were 19.02 +/- 19 months, mean duration of intubation and mechanical ventilation in DEX group was 5.17 +/- 4.58 days, and that in control group was 3.98 +/- 3.60 days. There was no significant difference between DEX and control group in the incidence of postextubation stridor [17% (5/30) vs. 10% (2/21); p = 0.5] and the reintubation rate [7% (2/30) vs. 10% (2/21); p = 0.7]. Our data revealed that the prophylactic use of dexamethasone in planned extubation of high risk children were not effective.

Role of dexamethasone in prevention of post extubation upper airway complications in paediatric patients in an intensive care unit

This prospective, randomized, double blind, placebo controlled study was undertaken to evaluate the role of dexamethasone in prevention of upper airway complications like laryngeal edema, stridor etc. A total of 60 children who were ventilated for more than 24 hours were included in the study. Patients were divided into two groups of 30 each. Group 1 received 0.5 mg/kg per dose of dexamethasone for 4 doses; 4 hours prior to extubation, at extubation, 6 and 12 hours after extubation respectively. There was statistically significant difference (p=0.019) between the two groups in relation to incidence of failed extubation. Laryngeal edema was more in group 2(63.33%) as compared to group 1(26.67%), the difference was statistically significant (P = 0.012). Thus it was concluded that use of dexamethasone was useful in preventing post extubation laryngeal edema/stridor in children and prophylactic use of dexamethasone also helps in reducing the incidence of failed extubation following prolonged ventilation.

Dexamethasone for reduction of nausea, vomiting and analgesic use after gynecological laparoscopic surgery

Objective: To evaluate the prophylactic use of dexamethasone for reducing postoperative nausea and vomiting (PONV) and analgesic use after gynecological laparoscopic surgery. Methods: In a prospective randomized, double-blind, placebo-controlled trial, 90 women received either intravenous placebo, 4 mg dexamethasone or 8 mg dexamethasone at the end of surgery. PONV and analgesic requirements were evaluated. Results: The rate of patients experiencing PONV within 24 h after anesthesia was 53% in the 4 mg dexamethasone group (P=0.3) and 20% in the 8 mg dexamethasone group (P=0.001), compared with the placebo group (63%). Requests for indomethacin to relieve intolerable pain were less in patients in the 8 mg dexamethasone group compared with the 4 mg dexamethasone (P= 0.047) or placebo (P= 0.029) groups. Conclusion: Prophylactic use of 8 mg dexamethasone is effective for reducing PONV and analgesic requirements after gynecological laparoscopic surgery.

Dexamethasone for reduction of nausea, vomiting and analgesic use after gynecological laparoscopic surgery

Objective To evaluate the prophylactic use of dexamethasone for reducing postoperative nausea and vomiting (PONV) and analgesic use after gynecological laparoscopic surgery. Methods In a prospective randomized, double-blind, placebo-controlled trial, 90 women received either intravenous placebo, 4 mg dexamethasone or 8 mg dexamethasone at the end of surgery. PONV and analgesic requirements were evaluated. Results The rate of patients experiencing PONV within 24 h after anesthesia was 53% in the 4 mg dexamethasone group ( P = 0.3) and 20% in the 8 mg dexamethasone group ( P = 0.001), compared with the placebo group (63%). Requests for indomethacin to relieve intolerable pain were less in patients in the 8 mg dexamethasone group compared with the 4 mg dexamethasone ( P = 0.047) or placebo ( P = 0.029) groups. Conclusion Prophylactic use of 8 mg dexamethasone is effective for reducing PONV and analgesic requirements after gynecological laparoscopic surgery.

The evolving role of pemetrexed (Alimta) in lung cancer

Pemetrexed (Alimta; Eli Lilly and Co, Indianapolis, IN) is a multitargeted antifolate that inhibits several folate-dependent enzymes that play roles in purine and pyrimidine synthesis. The principal toxicities of pemetrexed are neutropenia, diarrhea, nausea/vomiting, mucositis, and skin rash. These toxicities are more frequent in vitamin-deficient (folate and vitamin B 12 ) patients, and can be ameliorated by the co-administration of folate and vitamin B 12 . The use of prophylactic dexamethasone is also recommended to reduce the frequency of severe skin rash. Pemetrexed has significant single-agent activity in previously treated and untreated patients with non-small cell lung cancer (NSCLC). A recent phase III trial comparing pemetrexed with docetaxel in previously treated NSCLC patients showed equivalent efficacy with less bone marrow toxicity (eg, neutropenia) in the pemetrexed group. These results were pivotal in the approval of pemetrexed for the treatment of refractory NSCLC. Pemetrexed has been combined with the platinums (ie, cisplatin, carboplatin, and oxaliplatin) in NSCLC to yield clinical activity similar to that of other platinum-based doublets. A comparative phase III trial of cisplatin/pemetrexed against cisplatin/gemcitabine (Gemzar; Eli Lilly and Co) is under way. Pemetrexed has also been evaluated in combination with gemcitabine, and although the optimal dose and schedule of this combination has not been defined, clinical activity similar to other nonplatinum-based doublets has been observed. Preliminary evidence suggests that pemetrexed can be combined with thoracic radiation therapy, but more data are needed to evaluate the potential advantage(s) pemetrexed may have in this setting. Pemetrexed/platinum doublets also appear to possess activity in extensive stage small cell lung cancer. A phase II trial of single-agent pemetrexed is under way in both sensitive- and refractory-relapsed small cell lung cancer. Given the activity and excellent tolerability of pemetrexed, further studies in lung cancer are warranted.