A review of patients with advanced cervical cancer presenting to palliative care services at Queen Elizabeth Central Hospital in Blantyre, Malawi

Background Cervical cancer is the commonest cancer affecting women in Malawi, which has the highest rate of this disease in the world. Most cases are diagnosed at an advanced stage. Aim To describe the symptom burden, palliative care interventions, and outcomes of cervical cancer patients who entered care at Tiyanjane Clinic in Blantyre, Malawi, between January and December 2012. Methods We reviewed the case files of 72 patients presenting to our hospital-based palliative care service over one year. Results The mean age was 49.5 years. Twenty-six patients (36%) were HIVpositive and the majority of these (n = 22; 85%) were on antiretroviral medication at presentation to palliative care. Pain (n = 66; 92%), vaginal discharge (n = 44; 61%), and unpleasant odour (n = 37; 51%) were commonly reported. Over a third of patients (n = 26; 36%) reported pain in two or more sites. Fourteen patients (19%) reported vaginal bleeding. Spousal breakdown (through widowhood or divorce) was noted in over half (n = 41; 57%) of all cases. Pain relief was provided to 69 (96%) of the patients (morphine to 40 patients; 56%). Common interventions provided included metronidazole tablets (used vaginally), sanitary items, and counselling. At the end of the study period, 18 patients (25%) were still under the care of palliative services. Conclusions Access to medications such as morphine, metronidazole and tranexamic acid can improve quality of life, even when radiotherapy is limited. Health care teams require necessary skills and training, including how to perform a comprehensive assessment, with an emphasis on the provision of psychosexual counselling, to assist with the complexity of symptoms occurring in this vulnerable group.

Comparison of the eficacy and safety of 4 mg of ondansetron vs. 4 mg of nalbuphine for the treatment of neuraxial morphineinduced pruritus

Objective: To compare the eficacy and safety of 4 mg of ondansetron vs. 4 mg of nalbuphine for the treatment of neuraxial morphine-induced pruritus, in patients at the “Dr. José Eleuterio González” University Hospital from September 2012 to August 2013. Material and methods: A controlled, prospective, randomized study of 28 patients (14 per group) receiving neuraxial morphine analgesia was conducted, which was registered and approved by the ethics Committee of the Institution and patients agreed to participate in the study under informed consent. The results were segmented and contrasted (according to drug) by hypothesis testing; the association was determined by X2 with a 95% conidence interval (CI). Results: Pruritus was effectively resolved in both groups and no signiicant difference was found in the rest of the variables. An increase in the visual analogue scale (eVA) was observed at 6 and 12 hours for the ondansetron group, which was statistically signiicant (p≤0.05), however both groups had an eVA of less than 3. Conclusions: When comparing the eficacy and safety of ondansetron 4 mg vs. nalbuphine 4 mg for the treatment of neuraxial morphine induced pruritus, the only signiicant difference found was the mean eVA at 6 and 12 hours, favoring the ondansetron group. However, both groups scored less than 3 on the eVA. Therefore, we consider that both treatments are effective and safe in the treatment of pruritus caused by neuraxial morphine.

Manejo del dolor postoperatorio con morfina en anestesia espinal en cirugía gineco-obstétrica de la Fundación Pablo Jaramillo Crespo

Objetivo: Evaluar la eficacia del tratamiento del dolor postoperatorio con el uso de la morfina en anestesia conductiva en pacientes con cirugía ginecológica, obstétrica. Fundación Pablo Jaramillo Crespo; septiembre- diciembre de 2011. Métodos: Estudio observacional, analítico, prospectivo y cuantitativo. Se incluyeron, con la clasificación de la Sociedad Americana de Anestesiología (ASA) I y II a 231 pacientes, entre 15 y 65 años, hospitalizadas en la Fundación Pablo Jaramillo Crespo, por cirugía ginecológica-obstétrica, realizadas desde septiembre a diciembre de 2011. Se administraron dosis de morfina: 2 mg para epidural y 0,2 mg para anestesia raquídea. El dolor fue evaluado a las 12 y 24 horas, con la escala visual analógica de la intensidad del dolor (EVA). Resultados: La morfina utilizada no tuvo preservantes; se observó que la anestesia raquídea muestra una ligera ventaja a la epidural, con mejor tolerancia al dolor a las 12 y 24 horas (p<0.05) No hubo relación entre la etiología de las cirugías ginecológicas y obstétricas con el dolor a las 12 y 24 horas (p>0.05). En 25.78 % de los casos, la analgesia de la morfina, por administración raquídea, se complementó con el uso de ketorolaco por vía intravenosa. Un 49.2% de las pacientes no mostró efectos secundarios; de estos, los más observados fueron: el prurito (13.14 %), retención urinaria (11.3%), náuseas (9.8%) y vómitos (6.9%). Conclusión: el uso de morfina en dosis: 2 mg para epidural y 0.2 mg para anestesia raquídea, proporciona una favorable recuperación del dolor en las pacientes con cirugía ginecológica y obstétrica. Los efectos secundarios provocados por su administración pueden manejarse de manera eficiente sin alterar la recuperación postoperatoria

Trajectory of sedation assessment and sedative use in intubated and ventilated patients in intensive care: a clinical audit

Background: Sedation is crucial for the recovery of patients in intensive care units (ICUs). Maintaining comfort and safety promotes optimal care for critically ill patients. Purpose: To examine sedation assessment and management undertaken by health professionals for mechanically ventilated patients in one Australian ICU. Methods: A retrospective clinical audit was undertaken of medical records of all eligible, mechanically ventilated patients admitted to an ICU of an Australian metropolitan, teaching hospital over a 12-month period. A Sedation Audit Tool was used to collect data from the day of intubation to 5 days after intubation. Findings: Data were extracted from medical records of 150 patients. The Riker Sedation-Agitation Scale (SAS) was the scoring system used. Patients were unarousable or very sedated between 57% and 81% at some point during the study period, while between 5% and 11% were agitated, very agitated or extremely agitated across this time. Patients' sedation scores were not documented in between 3.3% and 23.3% of patients. Medications commonly used were propofol, midazolam, morphine, and fentanyl. There were 135 situations of adverse events, which related to patients pulling endotracheal tubes leading to malpositioning, patients biting endotracheal tubes causing desaturation, patient experiencing excessive agitation requiring restraint use, patients experiencing increased intracranial pressure above desired limits, patients self-extubating, and patients experiencing over-drowsiness leading to delays in extubation. Conclusions: Many patients were either very sedated or agitated at some point during the study period, and some patients experienced adverse outcomes associated with sedation practices. The findings inform future quality initiatives to improve sedation practices.

Covalent Protein Adduction by Drugs of Abuse

Recreational abuse of the drugs cocaine, methamphetamine, and morphine continues to be prevalent in the United States of America and around the world. While numerous methods of detection exist for each drug, they are generally limited by the lifetime of the parent drug and its metabolites in the body. However, the covalent modification of endogenous proteins by these drugs of abuse may act as biomarkers of exposure and allow for extension of detection windows for these drugs beyond the lifetime of parent molecules or metabolites in the free fraction. Additionally, existence of covalently bound molecules arising from drug ingestion can offer insight into downstream toxicities associated with each of these drugs. This research investigated the metabolism of cocaine, methamphetamine, and morphine in common in vitro assay systems, specifically focusing on the generation of reactive intermediates and metabolites that have the potential to form covalent protein adducts. Results demonstrated the formation of covalent adduction products between biological cysteine thiols and reactive moieties on cocaine and morphine metabolites. Rigorous mass spectrometric analysis in conjunction with in vitro metabolic activation, pharmacogenetic reaction phenotyping, and computational modeling were utilized to characterize structures and mechanisms of formation for each resultant thiol adduction product. For cocaine, data collected demonstrated the formation of adduction products from a reactive arene epoxide intermediate, designating a novel metabolic pathway for cocaine. In the case of morphine, data expanded on known adduct-forming pathways using sensitive and selective analysis techniques, following the known reactive metabolite, morphinone, and a proposed novel metabolite, morphine quinone methide. Data collected in this study describe novel metabolic events for multiple important drugs of abuse, culminating in detection methods and mechanistic descriptors useful to both medical and forensic investigators when examining the toxicology associated with cocaine, methamphetamine, and morphine.

Sucrose Bingeing Reduces the Reward Value of Sucrose

Binge eating occurs primarily on highly palatable food (PF) suggesting that the reward value of food has an important role in this behaviour. Bingeing also leads to reward dysfunction in rats and humans. The rewarding effect of binge eating may involve opioid mechanisms as opioid antagonists reduce PF consumption in animals that binge eat and binge eating produces neuroadaptations of opioid receptors in rodents. We tested this hypothesis by using the conditioned place preference (CPP) paradigm. First we established a sucrose CPP in male and female Long-Evans rats (n=8 for each group) using 1%, 5%, 15%, or 30% sucrose solution. Next, rats underwent the sucrose bingeing model in which separate groups of rats (n=8 for each group) received 12hr and 24hr access to 10% sucrose solution and chow, 12hr access to 0.1% saccharin solution and chow, or 12hr access to chow only every day for 28 days. Immediately following these sessions, rats were conditioned and tested in the CPP paradigm using a 15% sucrose solution. Finally, we examined whether the sucrose bingeing model altered morphine reward in female rats. Rats (n=8 for each group) received 12hr and 24hr access to 10% sucrose solution and chow every day for 28 days. Immediately following this access period, rats were conditioned to morphine (6mL/kg) or saline solution in the CPP paradigm and tested for a CPP. In all experiments, rats drank more sucrose solution than water during conditioning sessions. Male rats did not develop a CPP to any concentration of sucrose solution and females developed a CPP to 15% sucrose solution only. Following the sucrose bingeing protocol, sucrose CPP was attenuated in male rats that binged on sucrose and in all female rats. Sucrose bingeing in females did not affect the development of a CPP to morphine. These results suggest that sucrose consumption and sucrose CPP are measures of different psychological components of reward. Furthermore, sucrose bingeing reduces the rewarding effect of sucrose, but not morphine, suggesting that opioid reward is still intact.

An examination of verbal descriptors of cancer-induced bone pain and neuropathic cancer pain

Aims: The aim of the thesis was to identify verbal descriptors of cancer induced bone pain (CIBP) and neuropathic cancer pain (NCP). An examination of the verbal descriptors associated with these two pain syndromes further considered the relationship between common verbal descriptors, cancer type, performance status and analgesia. Methods: The project was conducted in two phases; Phase one was a systematic review of the literature to examine current evidence of verbal descriptors in CIBP and NCP. Phase two utilised secondary data analysis methodology. Data from 120 patients with confirmed CIBP and 61 patients with confirmed NCP were deemed eligible for entry into a de novo database for secondary analysis. Key descriptive data were considered such as gender, ECOG and pain scores to characterise the patient population. Verbal descriptors of CIBP and NCP were considered in detail across the secondary de novo database. Results: Gender was not identified as a diagnostic characteristic of CIBP and NCP with similar distribution across prevalence of pain reporting and also pain severity. Patients with breast (n=52,43.3%), prostate (n=35,29.2%) and lung (n=14,11.7%) cancer were found to be at an increased risk of CIBP. Those with NCP more was found more commonly among patients with breast cancer (n=21,34.4%). Patients with CIBP were found to have an ECOG performance of 1 (n=49, 40.8%) or 2 (n=43, 35.8%) which was lower than those with NCP with an ECOG of 0 (n=32, 52.5%) or 2 (n=18, 29.5%). Comparisons were made across analgesia and treatment options for CIBP and NCP. Patients with CIBP received a greater variety of treatment options including bisphosphonates and radiotherapy while patients with NCP were more commonly treated with analgesia alone. Patients with CIBP and NCP were taking strong opioids, however those with NCP (n=45, 73.8%) were more likely to utilise strong opioids than those with CIBP (n=61, 50.8%). It was noted that those with NCP required a daily morphine equivalence of almost 50% higher than those with CIBP. Average consumption of opioids was 155.6mg, for patients with NCP, compared to 76mg in patients with CIBP. Common verbal descriptors of CIBP and NCP were identified. The most common verbal descriptors for CIBP were aching, gnawing and throbbing and the most common verbal descriptors of NCP were aching, tender and sharp. Of the most common 6 descriptors for CIBP and NCP only one descriptor was unique to each pain type, gnawing for CIBP and stabbing for NCP. Conclusions: Patients with CIBP and NCP use similar verbal descriptors to characterise their pain with gnawing being unique to CIBP and stabbing being unique to NCP in the data considered within project. Further research is required to explore verbal descriptors which are both common and unique to CIBP and NCP. Further exploration of verbal descriptors would assist development of a comprehensive pain assessment tool which would enhance pain assessment for nurses, clinicians and patients.

An investigation into the suitability of time-of-flight mass spectrometry in forensic toxicology

Liquid chromatography coupled with mass spectrometry is one of the most powerful tools in the toxicologist’s arsenal to detect a wide variety of compounds from many different matrices. However, the huge number of potentially abused substances and new substances especially designed as intoxicants poses a problem in a forensic toxicology setting. Most methods are targeted and designed to cover a very specific drug or group of drugs while many other substances remain undetected. High resolution mass spectrometry, more specifically time-of-flight mass spectrometry, represents an extremely powerful tool in analysing a multitude of compounds not only simultaneously but also retroactively. The data obtained through the time-of-flight instrument contains all compounds made available from sample extraction and chromatography, which can be processed at a later time with an improved library to detect previously unrecognised compounds without having to analyse the respective sample again. The aim of this project was to determine the utility and limitations of time-of-flight mass spectrometry as a general and easily expandable screening method. The resolution of time-of-flight mass spectrometry allows for the separation of compounds with the same nominal mass but distinct exact masses without the need to separate them chromatographically. To simulate the wide variety of potentially encountered drugs in such a general screening method, seven drugs (morphine, cocaine, zolpidem, diazepam, amphetamine, MDEA and THC) were chosen to represent this variety in terms of mass, properties and functional groups. Consequently, several liquid-liquid and solid phase extractions were applied to urine samples to determine the most general suitable and unspecific extraction. Chromatography was optimised by investigating the parameters pH, concentration, organic solvent and gradient of the mobile phase to improve data obtained by the time-of-flight instrument. The resulting method was validated as a qualitative confirmation/identification method. Data processing was automated using the software TargetAnalysis, which provides excellent analyte recognition according to retention time, exact mass and isotope pattern. The recognition of isotope patterns allows excellent recognition of analytes even in interference rich mass spectra and proved to be a good positive indicator. Finally, the validated method was applied to samples received from the A& E Department of Glasgow Royal Infirmary in suspected drug abuse cases and samples received from the Scottish Prison Service, which we received from their own prevalence study targeting drugs of abuse in the prison population. The obtained data was processed with a library established in the course of this work.

Ketamina para el tratamiento de la hiperalgesia causada por remifentanil en cirugía: revisión sistemática de literatura

La hiperalgesia secundaria a la administración de remifentanil se ha documentado tanto en estudios animales como en estudios experimentales en humanos y ha aumentado su incidencia dado su uso cada vez más frecuente para el mantenimiento durante diferentes procedimientos anestésicos, anestesia general balanceada, anestesia total intravenosa y sedaciones. La hiperalgesia secundaria al uso de remifentanil es un proceso pro-nociceptivo relacionado pero que difiere de la tolerancia aguda, en el que los neurotransmisores excitatorios de N- metil D aspartato (NMDA) juegan un rol central. Por tanto la ketamina se ha utilizado en diferentes dosis para la prevención de dicha hiperalgesia sin que se haya establecido su efectividad para la prevención y tratamiento de esta condición. Se encontraron 8 estudios publicados en los últimos 10 años que proponen a la ketamina como una estrategia útil y efectiva el tratamiento de la hiperalgesia inducida por el uso de remifentanil. Los resultados demuestran que la ketamina es un tratamiento costo efectivo para el tratamiento de la hiperalgesia en diferentes poblaciones sometidas a diversos procedimientos quirúrgicos y anestésicos que incluyan la administración de remifentanil tanto en la inducción como en el mantenimiento anestésico sin generar efectos secundarios adicionales, así como que logra disminuir el consumo de opioides y la EVA en el posoperatorio.

Incidencia de síndrome de abstinencia secundario a opioides y/o benzodiacepinas en dos unidades de cuidados intensivos pediátricos

• Introducción: El síndrome de abstinencia (SA) es el conjunto de síntomas y signos que se producen al suspender bruscamente la administración de un fármaco una vez se haya establecido dependencia física. • Objetivos: Caracterizar los pacientes que presentan SA secundario a opiodes (OP) y/o benzodiacepinas(BZ) durante la hospitalización en las unidades de cuidados intensivos pediátricos de la Clínica Infantil Colsubsidio (CIC) y Hospital del Niño de Panamá (HDN) del 1 de abril al 30 de septiembre del 2016. • Materiales y métodos: se realizó un estudio descriptivo, longitudinal, prospectivo. Incluimos 189 pacientes en la CIC y 144 pacientes en el HDN. Se utilizó la escala SOPHIA para el diagnóstico de SA, las escalas COMFORT para evaluar la sedación en pacientes ventilados no relajados y la escala FLACC para evaluar la analgesia. Se utilizó software StataV12® para el análisis estadístico. • Resultados: se reportó una incidencia global de SA de 6.1/100 días personas. La incidencia acumulada de SA fue de 56.08% y 29.86% para la CIC y el HDN respectivamente. En la CIC el 69.81% de los pacientes que requirieron infusión de OP y BZ desarrollaron SA. Se reportó una dosis acumulada de fentanyl de 530.34 ± 276.49 mcg/kg. Con respecto al HDN, de los pacientes que recibieron opioides y benzodiacepinas el 53.49 % desarrollaron SA. • Conclusión: El SA secundario a opioides y/o benzodiacepinas es frecuente en nuestras unidades con una incidencia variable, es mayor la presentación del SA al usar ambos fármacos, mayores dosis acumuladas y más días de infusión continua.