Effect of low-dose ketamine on post-operative serum IL-6 production among elective surgical patients: a randomized clinical trial

Background: Surgery and Anesthesia cause an excessive pro-inflammatory response. Mulago Hospital is faced with staff shortage making post-operative pain management difficult.Interleukin-6 (IL-6) drives inflammatory pain, endothelial cell dysfunction and fibrogenesis. Ketamine is cheap and, readily available. We hypothesized that its attenuation of serum IL-6 was a surrogate for clinical benefit.Materials and methods: Institutional Review Board’s approval was sought and RCT was registered at clinical trials.gov (identifier number: NCT01339065). Consenting patients were randomized to receive pre-incision intravenous ketamine - 0.5mg/kg or 0.9% saline placebo in weighted dosing. Blood samples were collected and laboratory analyzed at baseline, post-operatively in PACU, 24 and 48 hours respectively.Results: We recruited 39 patients of whom 18 were randomized to the ketamine arm and 21 in the placebo arm with follow up at 24 and 48 hours. Serum IL-6 and IL-1β levels were analyzed using ELIZA assay of pre-coated micro wells. Ketamine suppressed serum IL-6 at PACU with reduced increase at 24 hours. There was no reaction in 98% of IL-1β assayed.Conclusion: Low-dose ketamine attenuated early serum IL-6 levels due to surgical response with reduced 24 hour increase, but the difference was not statistically significant and we recommend more studies.Keywords: Ketamine, post-operative inflammation, interleukin 6, interleukin 1-

Achieving the Recommended Endotracheal Tube Cuff Pressure: A Randomized Control Study Comparing Loss of Resistance Syringe to Pilot Balloon Palpation

Background. Both under- and overinflation of endotracheal tube cuffs can result in significant harm to the patient. The optimal technique for establishing and maintaining safe cuff pressures (20–30 cmH2O) is the cuff pressure manometer, but this is not widely available, especially in resource-limited settings where its use is limited by cost of acquisition and maintenance. Therefore, anesthesia providers commonly rely on subjective methods to estimate safe endotracheal cuff pressure. This study set out to determine the efficacy of the loss of resistance syringe method at estimating endotracheal cuff pressures. Methods. This was a randomized clinical trial. We enrolled adult patients scheduled to undergo general anesthesia for elective surgery at Mulago Hospital, Uganda. Study participants were randomized to have their endotracheal cuff pressures estimated by either loss of resistance syringe or pilot balloon palpation. The pressures measured were recorded. Results. One hundred seventy-eight patients were analyzed. 66.3% (59/89) of patients in the loss of resistance group had cuff pressures in the recommended range compared with 22.5% (20/89) from the pilot balloon palpation method. This was statistically significant. Conclusion. The loss of resistance syringe method was superior to pilot balloon palpation at administering pressures in the recommended range. This method provides a viable option to cuff inflation

Effect of low-dose ketamine on post-operative serum IL-6 production among elective surgical patients: a randomized clinical trial.

Background: Surgery and Anesthesia cause an excessive pro-inflammatory response. Mulago Hospital is faced with staff shortage making post-operative pain management difficult.Interleukin-6 (IL-6) drives inflammatory pain, endothelial cell dysfunction and fibrogenesis. Ketamine is cheap and, readily available. We hypothesized that its attenuation of serum IL-6 was a surrogate for clinical benefit. Materials and methods: Institutional Review Board\u2019s approval was sought and RCT was registered at clinical trials.gov (identifier number: NCT01339065). Consenting patients were randomized to receive pre-incision intravenous ketamine - 0.5mg/kg or 0.9% saline placebo in weighted dosing. Blood samples were collected and laboratory analyzed at baseline, post-operatively in PACU, 24 and 48 hours respectively. Results: We recruited 39 patients of whom 18 were randomized to the ketamine arm and 21 in the placebo arm with follow up at 24 and 48 hours. Serum IL-6 and IL-1\u3b2 levels were analyzed using ELIZA assay of pre-coated micro wells. Ketamine suppressed serum IL-6 at PACU with reduced increase at 24 hours. There was no reaction in 98% of IL-1\u3b2 assayed. Conclusion: Low-dose ketamine attenuated early serum IL-6 levels due to surgical response with reduced 24 hour increase, but the difference was not statistically significant and we recommend more studies

Clinical Study Analgesic Effects of Preincision Ketamine on Postspinal Caesarean Delivery in Uganda's Tertiary Hospital: A Randomized Clinical Trial

Background. Good postoperative analgesic management improves maternal satisfaction and care of the neonate. Postoperative pain management is a challenge in Mulago Hospital, yet ketamine is accessible and has proven benefit. We determined ketamine's postoperative analgesic effects. Materials and Methods. We did an RCT among consenting parturients that were randomized to receive either intravenous ketamine (0.25 mg/kg) or placebo after spinal anesthetic. Pain was assessed every 30 mins up to 24 hours postoperatively using the numerical rating scale. The first complaint of pain requiring treatment was noted as "time to first breakthrough pain." Results. We screened 100 patients and recruited 88 that were randomized into two arms of 44 patients that received either ketamine or placebo. Ketamine group had 30-minute longer time to first breakthrough pain and lower 24-hour pain scores. Postoperative diclofenac consumption was lesser in the ketamine group compared to placebo and Kaplan-Meier graphs showed a higher probability of experiencing breakthrough pain earlier in the placebo group. Conclusion. Preincision intravenous ketamine (0.25 mg/kg) offered 30-minute prolongation to postoperative analgesia requirement with reduced 24-hour pain scores. We recommend larger studies to explore this benefit. This trial is registered with Pan African Clinical Trial Registry number PACTR201404000807178

Uganda Genome Resource : A rich research database for genomic studies of communicable and non-communicable diseases in Africa

Summary The Uganda Genome Resource (UGR) is a well-characterized genomic database with a range of phenotypic communicable and non-communicable diseases and risk factors generated from the Uganda General Population Cohort (GPC), a population-based open cohort established in 1989. The UGR comprises genotype data on ∼5,000 and whole-genome sequence data on ∼2,000 Ugandan GPC individuals from 10 ethno-linguistic groups. Leveraging other platforms at MRC/UVRI and LSHTM Uganda Research Unit, there is opportunity for additional sample collection to expand the UGR to advance scientific discoveries. Here, we describe UGR and highlight how it is providing opportunities for discovery of novel disease susceptibility genetic loci, refining association signals at new and existing loci, developing and testing polygenic scores to determine disease risk, assessing causal relations in diseases, and developing capacity for genomics research in Africa. The UGR has the potential to develop to a comparable level of European and Asian large-scale genomic initiatives

Genome-wide association analysis of cystatin-C kidney function in continental Africa

BACKGROUND: Chronic kidney disease is becoming more prevalent in Africa, and its genetic determinants are poorly understood. Creatinine-based estimated glomerular filtration rate (eGFR) is commonly used to estimate kidney function, modelling the excretion of the endogenous biomarker (creatinine). However, eGFR based on creatinine has been shown to inadequately detect individuals with low kidney function in Sub-Saharan Africa, with eGFR based on cystatin-C (eGFRcys) exhibiting significantly superior performance. Therefore, we opted to conduct a GWAS for eGFRcys. METHODS: Using the Uganda Genomic Resource, we performed a genome-wide association study (GWAS) of eGFRcys in 5877 Ugandans and evaluated replication in independent studies. Subsequently, putative causal variants were screened through Bayesian fine-mapping. Functional annotation of the GWAS loci was performed using Functional Mapping and Annotation (FUMA). FINDINGS: Three independent lead single nucleotide polymorphisms (SNPs) (P-value 99%. The rs911119 SNP maps to the cystatin C gene and has been previously associated with eGFRcys among Europeans. With gene-set enrichment analyses of the olfactory receptor family 51 overlapping genes, we identified an association with the G-alpha-S signalling events. INTERPRETATION: Our study found two previously unreported associated SNPs for eGFRcys in continental Africans (rs59288815 and rs4277141) and validated a previously well-established SNP (rs911119) for eGFRcys. The identified gene-set enrichment for the G-protein signalling pathways relates to the capacity of the kidney to readily adapt to an ever-changing environment. Additional GWASs are required to represent the diverse regions in Africa. FUNDING: Wellcome (220740/Z/20/Z)

A comparison of all-cause and cause-specific mortality by household socioeconomic status across seven INDEPTH network health and demographic surveillance systems in sub-Saharan Africa

Background: Understanding socioeconomic disparities in all-cause and cause-specific mortality can help inform prevention and treatment strategies. Objectives: To quantify cause-specific mortality rates by socioeconomic status across seven health and demographic surveillance systems (HDSS) in five countries (Ethiopia, Kenya, Malawi, Mozambique, and Nigeria) in the INDEPTH Network in sub-Saharan Africa. Methods: We linked demographic residence data with household survey data containing living standards and education information we used to create a poverty index. Person-years lived and deaths between 2003 and 2016 (periods varied by HDSS) were stratified in each HDSS by age, sex, year, and number of deprivations on the poverty index (0–8). Causes of death were assigned to each death using the InterVA-4 model based on responses to verbal autopsy questionnaires. We estimated rate ratios between socioeconomic groups (2–4 and 5–8 deprivations on our poverty index compared to 0–2 deprivations) for specific causes of death and calculated life expectancy for the deprivation groups. Results: Our pooled data contained almost 3.5 million person-years of observation and 25,038 deaths. All-cause mortality rates were higher among people in households with 5–8 deprivations on our poverty index compared to 0–2 deprivations, controlling for age, sex, and year (rate ratios ranged 1.42 to 2.06 across HDSS sites). The poorest group had consistently higher death rates in communicable, maternal, neonatal, and nutritional conditions (rate ratios ranged 1.34–4.05) and for non-communicable diseases in several sites (1.14–1.93). The disparities in mortality between 5–8 deprivation groups and 0–2 deprivation groups led to lower life expectancy in the higher-deprivation groups by six years in all sites and more than 10 years in five sites. Conclusions: We show large disparities in mortality on the basis of socioeconomic status across seven HDSS in sub-Saharan Africa due to disparities in communicable disease mortality and from non-communicable diseases in some sites. Life expectancy gaps between socioeconomic groups within sites were similar to the gaps between high-income and lower-middle-income countries. Prevention and treatment efforts can benefit from understanding subpopulations facing higher mortality from specific conditions

Postoperative pain after cesarean section: assessment and management in a tertiary hospital in a low-income country

Background: There is little information about the current management of pain after obstetric surgery at Mulago hospital in Uganda, one of the largest hospitals in Africa with approximately 32,000 deliveries per year. The primary goal of this study was to assess the severity of post cesarean section pain. Secondary objectives were to identify analgesic medications used to control post cesarean section pain and resultant patient satisfaction. Methods: We prospectively followed 333 women who underwent cesarean section under spinal anesthesia. Subjective assessment of the participants’ pain was done using the Visual Analogue Scale (0 to 100) at 0, 6 and 24 h after surgery. Satisfaction with pain control was ascertained at 24 h after surgery using a 2-point scale (yes/no). Participants’ charts were reviewed for records of analgesics administered. Results: Pain control medications used in the first 24 h following cesarean section at this hospital included diclofenac only, pethidine only, tramadol only and multiple pain medications. There were mothers who did not receive any analgesic medication. The highest pain scores were reported at 6 h (median: 37; (IQR:37.5). 68% of participants reported they were satisfied with their pain control. Conclusion: Adequate management of post-cesarean section pain remains a challenge at Mulago hospital. Greater inter-professional collaboration, self-administered analgesia, scheduled prescription orders and increasing availability of analgesic drugs may contribute to improved treatment of postoperative pain with better pain scores.Medicine, Faculty ofNon UBCAnesthesiology, Pharmacology and Therapeutics, Department ofReviewedFacult