The Effect of Intravenous Ketamine After Spinal Anesthesia on the Duration of Postoperative Analgesia and Analgesic Requirement

Objective: To evaluate the impact of ketamine following spinal anesthesia on the duration of postoperative analgesia and the need for analgesics. Methods: This was a prospective, randomized, double-blinded placebo-controlled study done over a period of two years. A total of 60 participants undergoing elective surgeries under spinal anesthesia were randomized into two groups. After 10 min of spinal anesthesia and achieving the required level of sensory and motor blockade, both groups were given Inj. Midazolam 1 mg intravenously, followed by Inj. Ketamine 0.25 mg/kg, volume made up to 10 mL with normal saline, given intravenously for Group K and Inj. Normal Saline 10 mL was given intravenously for Group N. Hemodynamic monitoring was done intraoperatively, and the postoperative visual analog score (VAS), sedation score, the mean time for the first rescue analgesia, and the total dose of postoperative analgesic required in 24 h were tabulated. Results: There was no statistical difference between the two groups in terms of age, weight, ASA grade, and duration of surgery. In Group K, the VAS scores were significantly lower and patients were comfortable when compared to Group N (P value <.01). The mean time to first rescue analgesia was longer in Group K (6.4 ± 1.69 h) when compared to Group N (2.9 ± 1.01 h), and the total dose of postoperative analgesia (Tramadol) required in 24 h was also significantly less in Group K (143.33 ± 56.83 mg) when compared to Group N (236 ± 49.01 mg). Changes in hemodynamic parameters (heart rate and mean arterial pressure (MAP)) were statistically and clinically not significant in both the intraoperative and postoperative periods between the groups. Conclusion: Patients in Group K were more comfortable, had a longer duration of postoperative analgesia, and required less dose of rescue analgesia in the postoperative period. Ketamine is a safe drug that is readily available, and it decreases the use of opioids and opioid-related side effects. Therefore, ketamine can serve effectively as an adjunctive analgesic drug.

Adherence to antiretroviral therapy & its determinants amongst HIV patients in India.

BACKGROUND & OBJECTIVE: Very high levels of adherence are required for ART to be effective. There is limited information available from India on adherence to ART and its predictors. We carried out this study to examine adherence levels and to explore the factors associated with adherence among PLHA receiving ART in India. METHODS: Using a cross-sectional study design 310 HIV+ patients receiving ART (252 paying out-of-pocket; 58 free via employee-insurance programme) were interviewed from Pune and Delhi health facilities, using a semi-structural questionnaire. RESULTS: The median age for patients was 36 yr. The median time from diagnosis of HIV-infection was 34.5 months, median time on ART was 16 months and median CD4 cell count at start of ART was 110 cells/microl. 98 per cent of the respondents were using a non protease inhibitor (PI) treatment regimen. Mean 4-day adherence was 93 per cent. Adherence was lower over longer periods of recall: 20 per cent reported missed does over the past 7 days; 33 per cent reported ever missing a full day's medications and 16 per cent had a treatment interruption of more than 7-days at least once. On univariate analysis less than university education, being unemployed, obtaining free treatment, severe depression, baseline CD4 count>200/microl, hospitalization >2 times, having moderate to severe side-effects and taking 4 or more medicines were associated with lower adherence (<90%). However, only obtaining free treatment (adjusted OR, 4.05, 95% CI 1.42-11.54, P=0.009) and severe depression (adjusted OR 4.48, 95% CI 1.64-12.27, P=0.003) were associated with lower adherence in multivariate analysis. INTERPRETATION & CONCLUSION: Although the overall adherence was high, lower levels of adherence were documented among patients receiving free ART. Provision of free treatment without adequate patient preparation and adherence support may compromise the success of ART scale up programmes. Early diagnosis and management of depression need special focus.

Nevirapine versus efavirenz based antiretroviral treatment in naive Indian patients: comparison of effectiveness in clinical cohort.

OBJECTIVE: Our objective was to compare immunologic effectiveness of nevirapine and efavirenz based antiretroviral therapy in antiretroviral naïve HIV-1 infected Indian patients. DESIGN AND METHODS: Study was an observational, non-randomized, longitudinal cohort. Antiretroviral naive HIV-1 infected patients receiving efavirenz + 2NRTI (n=254) and nevirapine + 2 NRTI (n=857) from April 2000 were followed up at two tertiary care HIV clinics at Ahmedabad and Pune. Patients were followed up clinically monthly and CD4 was carried out every 3 monthly. All patients were examined for various side effects as well as development of various OIs. Data were analyzed using standard statistical methods. RESULTS: Baseline characteristics for both the groups (NVP and EFV) were comparable. In the random effects model, there was an increase of 40.97 (p < 0.05) units of CD4 cell counts with an unit increase in time in the NVP arm as against a 44.75 (p < 0.05) units of increase in CD4 cell counts in the EFV group with a unit increase in time, which is significant for both groups. However, at any given point of time there was no difference in the rate of increase of CD4 count between the two treatment arms (p = 0.58). Hypersensitivity reaction (6.6% in NVP vs. 2.32% in EFV, p = 0.0146) and hepatitis (3.2% in NVP vs. 0% in EFV, p = 0.0085) were more common with nevirapine, while neurologic disturbances (0.93% in NVP vs. 20.15% in EFV, p = 0.0001) were more common with efavirenz. Incidence of distal sensory neuropathy and lipid abnormalities was similar in both the groups. CONCLUSION: Use of NVP and EFV based HAART in antiretroviral naive Indian patients led to significant and durable rise in CD4 cell count. Although observational and non-randomized, our study showed equivalent immunological response amongst NVP and EFV based HAART which is in line with the results of the 2NN study.

API consensus guidelines for use of antiretroviral therapy in adults (API-ART guidelines). Endorsed by the AIDS Society of India.

With rational use of antiretroviral therapy (ART), human immunodeficiency virus (HIV) infection has been transformed into a chronic manageable illness like diabetes and hypertension. These guidelines provide information on state of art, evidence based approach for use of ART in Indian context. When to initiate ART? Antiretroviral therapy is indicated for all symptomatic HIV infected persons regardless of CD4 counts and plasma viral load (PVL) levels. In asymptomatic patients, ART should be offered when the CD4 counts < 200/mm3 and should be considered in patients with CD4 counts between 200-250/mm3. Therapy is not recommended for patients with CD4 count more than 350/ mm3. Involvement of patient in all treatment decisions and assessing readiness is critical before initiating ART. What to start with? A non-nucleoside reverse transcriptase inhibitor (NNRTI) based regimen is recommended for antiretroviral naïve patients. The choice between nevirapine and efavirenz is based on differences in adverse events profiles; cost and availability of convenient fixed dose combinations and need for concomitant use of rifampicin. A backbone of 2-nucleoside reverse transcriptase inhibitors (NRTIs) is combined with the NNRTI. Various combinations and ART strategies not to be used in clinical practice has been enlisted. How to follow up? Recommendations have been made for baseline evaluation and monitoring of patients on ART. These include guidelines on laboratory and clinical evaluation. A plasma viral load at 6 months after initiation of first-line ART is strongly recommended. Yearly estimation of lipid profile has been recommended. How to identify and manage ART failure? The guidelines recognize the issue of identifying ART failure late if only CD4 counts are used for monitoring. In the absence of resistance testing various second-line regimens have been enlisted. A boosted protease inhibitor based regimen is recommended in this situation to be combined with 2-NRTIs. Special situations Recommendations have been made for use of ART in HIV-TB, HIV-HBV, and HIV-HCV co-infected patients. In patients with active TB and a CD4 count < 200/mm3, initiation of ART is recommended as soon as the anti-TB treatment is tolerated. Efavirenz is the only ARV drug, which can be safely used with rifampicin. In pregnancy use of single dose nevirapine for reducing risk of mother to child transmission of HIV is not recommended, because of the risk of development of resistance. For post-exposure prophylaxis taking ART treatment history of the source patient is crucial in designing an effective regimen.

Neurological manifestations of HIV disease.

We report the results of neurological evaluation of 1,527 HIV positive subjects. Neurological complications were seen in 457 patients (481 neurological events). The prevalence was 20.24% of patients attending the out-patient clinic and in 44.57% of in-patients. Involvement of all levels of neuraxes was documented. The commonest manifestations were neuropathies, including herpes zoster (28.27%), meningitis (17.88%) and mass lesions (16%). Cryptococcal meningitis was clearly commoner than tubercular meningitis (67.44% vs 18.60% of all cases of meningitis, respectivelv). Amongst mass lesions, 14/24 single lesions and 27/38 multiple lesions responded to anti-toxoplasma treatment and were diagnosed as CNS toxoplasmosis. In abscence of biopsy, it would be prudent to initiate empirical anti-toxoplasma treatment for all HIV patients with mass lesions and assess clinical and radiological response. To our knowledge this is the largest series of neurological manifestations of HIV disease documented in Indian literature.