Patient Evaluation of Patient-Controlled Analgesia for Pain Crises in Sickle Cell Disease.

BACKGROUND: Vaso-occlusive crisis causing severe pain can be seen in patients with sickle cell anemia and potent opioids should be used in this process. Although sickle cell disease (SCD) patients use patient-controlled analgesia (PCA), we encountered no study evaluating this method from the participants' perspective. AIM: This descriptive study aimed to evaluate the use and effectiveness of PCA administered using the Mersin Algology Protocol (MAP) during painful episodes of SCD based on participants reports. METHODS: After obtaining approval from the local ethics committee, 109 SCD participants using PCA as per the MAP between 2018 and 2020 were recruited for the study. The participants answered a 28-item questionnaire regarding their annual number of pain crises, sites of pain, knowledge about PCA, the number of times they used PCA, and the positive and negative aspects of the PCA method. RESULTS: The mean age of the participants was 28.80 ± 11.5 years. Ninety-nine (90.8%) of the participants considered PCA superior to other pain management methods they had used previously. The 53 participants (48.6%) who waited for their pain to worsen before administering the demand dose expressed fear of taking high doses of medication. As the number of times a participant used PCA increased, NRS scores for pain at the time of demand dosing decreased from 7-10 to 4-6 (p = .013). Eighty-five (78%) of the participants reported having no problems related to the device or drug while using PCA. CONCLUSION: We found that PCA was used more correctly by participants with more experience using the device. Participants who delay demand dosing do so because of anxiety about developing dependence and to avoid high doses.

[Pain management in sickle cell disease]. / Schmerztherapie bei Sichelzellkrankheit.

Sickle cell disease is associated with numerous symptoms and complications. Acute painful crisis is the most characteristic manifestation of the disease. In addition, many patients report chronic pain. As both acute and chronic pain severely diminish quality of life, adequate pain management is crucial. Recommendations for the treatment of acute painful crises are based on the World Health Organization analgesic ladder, which has been developed for cancer-related pain. Chronic pain can be treated with basic long-acting opioids and on-demand short-acting opioids. If patients show signs of neuropathic pain, administration of anticonvulsants, antidepressants or possibly ketamine should be considered.

Serum zinc level during and after acute painful episodes in children with sickle cell anemia at the aminu kano teaching hospital, Kano, Northern Nigeria.

BACKGROUND: Acute painful crisis due to vaso-occlusive event is the leading cause of hospitalization in patients with sickle cell anemia (SCA). Zinc deficiency in children with SCA is associated with increased frequency and severity of acute painful events. We determined serum zinc level in children with SCA during acute painful crisis and compared the same with children with SCA who are in steady state and healthy non-sickle cell disease children. SUBJECTS AND METHODS: This was a descriptive longitudinal study, involving children with SCA age 6 months to 15 years at Aminu Kano Teaching Hospital, Kano, Northern Nigeria. Subjects were recruited into three groups, which consisted of SCA in acute painful crisis, SCA in steady state, and normal subjects with hemoglobin AA (HbAA). A total of 210 subjects were recruited, 70 subjects each for SCA in acute painful crisis, SCA in steady state, and HbAA groups, respectively. Serum zinc was analyzed with atomic absorption spectrophotometery. Serum zinc levels were repeated in children with SCA and acute painful crisis 4 weeks after resolution of painful events. RESULTS: The mean serum zinc level of SCA with acute painful crisis was higher than SCA in steady state, but the difference was not statistically significant (24.4 [11.0] and 23.4 [7.4]) µg/dL, respectively (t = 16.04, P = 0.54). While the HbAA control had significantly higher mean serum zinc level than SCA groups, both in acute painful and in steady state (F = 59.3, P = 0.001). Among children with SCA and acute painful crisis, repeat serum zinc level 4 weeks after resolution of acute painful events was significantly higher than during pain crisis (t = 64, P = 0.001). CONCLUSION: Zinc deficiency occurs in children with SCA and the deficiency is worsened by acute painful events Therefore, it is recommended that zinc level should be assessed and any deficiency treated. Supplementation of zinc should also be enhanced as this may reduce painful crisis in SCA.

Opioid Utilization by Pregnant Women with Sickle Cell Disease and the Risk of Neonatal Abstinence Syndrome.

BACKGROUND: Pregnant women with sickle cell disease (SCD) are at increased risk of maternal and fetal complications. There are limited data on the outcome of the treatment of VOCs with opioids in relation to neonatal complications during pregnancy. METHODS: This is a retrospective cohort study of women with SCD from January 1999 to December 2008. Women with SCD were identified by ICD-9 codes and matched 2:1 to a control group of women on methadone for opioid dependence. The primary outcome was the rate of neonatal abstinence syndrome (NAS). Secondary outcomes included the mean NAS score prior to treatment and the length of treatment. Statistical analysis was performed using SPSS. RESULTS: Twenty-one women with SCD who delivered a total of 23 neonates were included. The rate of NAS among infants born to women with SCD who were treated with opioids at any time was 22% compared to 54% in the methadone controls (p = .010). The rate of NAS was 27% among infants born to women taking opioids daily compared to 54% in the methadone control group (p = .062). CONCLUSIONS: Neonates born to women with SCD who are treated with daily opioids are at a similar risk for developing NAS as those born to mothers on methadone for opioid dependence. Neonates born to women with SCD treated with episodic opioids are at a significantly lower risk for developing NAS than those born to women on methadone for opioid dependence.

East Mediterranean region sickle cell disease mortality trial: retrospective multicenter cohort analysis of 735 patients.

Sickle cell disease (SCD), one of the most common genetic disorders worldwide, is characterized by hemolytic anemia and tissue damage from the rigid red blood cells. Although hydroxyurea and transfusion therapy are administered to treat the accompanying tissue injury, whether either one prolongs the lifespan of patients with SCD is unknown. SCD-related mortality data are available, but there are few studies on mortality-related factors based on evaluations of surviving patients. In addition, ethnic variability in patient registries has complicated detailed analyses. The aim of this study was to investigate mortality and mortality-related factors among an ethnically homogeneous population of patients with SCD. The 735 patients (102 children and 633 adults) included in this retrospective cohort study were of Eti-Turk origin and selected from 1367 patients seen at 5 regional hospitals. A central population management system was used to control for records of patient mortality. Data reliability was checked by a data supervision group. Mortality-related factors and predictors were identified in univariate and multivariate analyses using a Cox regression model with stepwise forward selection. The study group included patients with homozygous hemoglobin S (Hgb S) disease (67 %), Hb S-ß(0) thalassemia (17 %), Hgb S-ß(+) thalassemia (15 %), and Hb S-α thalassemia (1 %). They were followed for a median of 66 ± 44 (3-148) months. Overall mortality at 5 years was 6.1 %. Of the 45 patients who died, 44 (6 %) were adults and 1 (0.1 %) was a child. The mean age at death was 34.1 ± 10 (18-54) years for males, 40.1 ± 15 (17-64) years for females, and 36.6 ± 13 (17-64) years overall. Hydroxyurea was found to have a notable positive effect on mortality (p = 0.009). Mortality was also significantly related to hypertension and renal damage in a univariate analysis (p = 0.015 and p = 0.000, respectively). Acute chest syndrome, splenic sequestration, and prolonged painful-crisis-related multiorgan failure were the most common causes of mortality. In a multivariate analysis of laboratory values, only an elevated white blood cell count was related to mortality (p = 0.009). These data show that despite recent progress in the treatment of SCD, disease-related factors continue to result in mortality in young adult patients. Our results highlight the importance of evaluating curative treatment options for patients who have an appropriate stem cell donor in addition to improving patient care and patient education.

Hospitalization Events Among Adolescents and Adults With Sickle Cell Disease in a Tertiary Care Center in Central India.

BACKGROUND: Sickle cell disease (SCD) is an inherited red blood cell disorder, wherein mutation causes the substitution of glutamic acid to valine at the sixth position of the ß-globin chain. These include sickle cell anemia (homozygous sickle mutation), sickle-beta thalassemia, and hemoglobin SCD. The clinical manifestations of SCD are protean. Individuals with SCD suffer from both acute and chronic complications, which include recurring episodes of pain commonly called vaso-occlusive crisis (VOC) - acute chest syndrome (ACS); aseptic necrosis of the bone; micro-infarction of the spleen, brain, and kidney; infections; stroke; and organ damage affecting every part of the body. SCD necessitates frequent hospitalizations because of severe complications, which pose a significant burden on caregivers and economic strain on healthcare systems. The pattern of hospital admission with SCD varies in different parts of the world. OBJECTIVE: This study aimed to determine the causes of hospitalization among adolescent and adult patients with SCD and to determine factors associated with their hospital stay. METHODS: The study was a hospital-based prospective observational study comprising adolescent and adult patients diagnosed with SCD, aged 15-45 years, who were hospitalized in the Department of General Medicine at All India Institute of Medical Sciences in Raipur from August 2021 to August 2022. RESULT: According to our study, the primary reason for hospitalization was a painful crisis, accounting for 63% of cases, followed by infection (17%), ACS (11%), and acute hemolytic crisis (9%). Notably, we did not observe any significant differences between genders and causes of admission (p > 0.05). Joint pain (p = 0.005), back pain (p = 0.001), and chest pain (p = 0.001) were more frequently reported by adults over the age of 19. In addition, our analysis of the duration of hospital stays and various factors revealed that patients admitted for infections had a significantly longer mean hospital stay duration (p = 0.040). CONCLUSION: Acute painful crises were the primary cause of hospital admission among individuals with SCD; many patients also encountered infections and ACS. Furthermore, patients who experienced infections and VOC had a lengthier duration of hospital stay. Therefore, it is essential to provide them with comprehensive instructions on various preventive measures against infections and the factors that trigger painful crises.

Impact of Imatinib on reducing the painful crisis in patients with sickle cell disease.

INTRODUCTION: Sickle cell disease (SCD) is a common hemoglobinopathy worldwide that causes painful crises and hospitalization of patients. These attacks decrease survival and cause chronic end-organ damage in these patients. HYPOTHESIS: For this reason, finding new treatment approaches could be helpful. METHOD: In this study, Imatinib was applied as a mast cell inhibitor to reduce pain crises in these patients. Seven patients resistant to hydroxyurea and folic acid treatment and who had at least four painful crises per year with hospitalization were enrolled in this study with treatment with Imatinib (100 mg, twice daily). Subsequently, the number and duration of hospitalizations, analgesic requirement, the severity of chronic pain, and changes in the hematological parameters of these patients were evaluated before and after the treatment. RESULTS: The data showed that the total number of hospitalizations and the entire duration of hospitalizations were reduced 16 times after treatment with Imatinib, without apparent changes in hematological parameters. Also, the demand for pethidine, tramadol, and nonsteroidal anti-inflammatory drugs (NSAIDs) was reduced in all patients. The average reduction in chronic pain was over 70%. CONCLUSION: This study demonstrates that treatment with Imatinib in patients with SCD or sickle cell anemia (SCA) may be a suitable therapeutic option for reducing painful crises.

Management of fever and acute painful crises in children with sickle cell disease in emergency departments: a tertiary hospital experience.

Sickle Cell Disease (SCD) is highly prevalent in Saudi Arabia with variable demographics and access to health care facilities including emergency departments. Literature reviews for locally published articles are deficient in the in-depth evaluation of current emergency practices in managing patients with SCD. The study aims to assess the current emergency practice in managing SCD patients in tertiary hospitals. We reviewed data of 212 visits by patients with SCD over three years and assessed the current emergency department practices in managing common SCD crises, such as vaso-occlusive (VOC) and febrile episodes. Our findings revealed that 47.2%, 37.7%, and 15% of the patients presented with pain, fever, or both, respectively. The patients were triaged level III according to the Canadian triage and acuity scale system in 89% of the visits. The Median time for patients to see healthcare providers was 22 min. In the first 2 h, 86% of the patients received at least one fluid bolus and 79% of them received appropriate analgesia for pain crises. Approximately 41.5% of the patients with fever were admitted and received ceftriaxone as single intravenous antimicrobial agent. However, none of the patients had bacteremia. Only 2.4% of the patients had either urinary tract infection or osteomyelitis based on imaging. ED management is a key factor in the successful management of patients with SCD in a timely manner by providing fluids, analgesia, and antibiotics. Adopting evidence-based guidelines and avoiding unnecessary admissions are suggested in clinically well patients with fever in the era of completed vaccination, antibiotic prophylaxis, and good access to care for patients with a clear viral infection focus.

Treatment Options That Reduce the Duration of Sickle Cell Vaso-Occlusive Crises: A Systematic Review.

Most patients with sickle cell disease (SCD) seek hospital care because of pain symptoms. While some patients opt to treat themselves at home, some prefer to seek treatment in a hospital setting. There are, however, some patients with more complicated effects of the disease who seek treatment so often that they have been termed "super-users." This paper seeks to determine, across the board, the treatments available for vaso-occlusive crisis (VOC), the most common complication of SCD. Due to the frequency and unpredictable nature of VOC, it is no surprise that the lives of so many patients dealing with SCD are constantly disrupted by this complication. Treatments that reduce the frequency of VOC and the need for hospital admissions will help these patients find some semblance of balance in their quality of life.

Antibiotics to modify sickle cell disease vaso-occlusive crisis?

Despite the availability of hydroxyurea, the clinical use of the medication among patients with sickle cell disease (SCD) remains low in the United States. Given the high healthcare utilization cost, SCD requires new therapeutic approaches. Recent studies demonstrated bacterial overgrowth and dysbiosis-related intestinal pathophysiological changes in SCD. Intestinal microbes regulate neutrophil ageing. Aged and activated neutrophils contribute to the pathogenesis of vaso-occlusive crisis (VOC) in SCD. In this paper, we will review the pre-clinical and clinical data on how antibiotics might reduce the intestinal microbial density and influence the course of VOC. Based on these observations, we will discuss rationales for and potential challenges to antibiotic-based therapeutic approaches that may modify the clinical course of VOC in SCD.

Clinical and Laboratory Predictors of Painful Vaso-Occlusive Crisis Among Sickle Cell Disease Patients: A Single-Center Study in Saudi Arabia.

Introduction Vaso-occlusive crisis (VOC) episodes are considered to be the cause of 95% of hospitalizations for sickle cell disease (SCD) patients. The frequency of VOC is significantly associated with higher or lower lactate dehydrogenase levels, higher hemoglobin concentration, higher white blood cell, and neutrophil count, and lower platelet counts. In this study, we highlighted the association and predictors of VOC episodes in Saudi Arabia. Methods This is a retrospective observational study that was conducted in a period from January 2018 to December 2019 which included patients who were admitted and treated as sickle cell disease patients were included in this study. Retrieved data included patients' age, sex, and other demographic data items as well as the clinical history of SCD. The patients were divided into two groups. Those patients who developed one or two VOC episodes in the period between 2018-2019 were considered mild in severity and patients who developed three or more VOC episodes in the period between 2018-2019 were categorized as moderate to severe. Results A total of ninety-four patients (58 males and 36 females) with a male to female ratio of 1.6 were included in this study. The prevalence of patients who had severe vaso-occlusive crisis was 39.4% while mild-moderate were detected among 60.6% of the patients. It was found that there was no significant difference between the frequency of vaso-occlusive crisis and all the hematological parameters (all p>0.05). It was found that the risk of having vaso-occlusive crisis for those patients who were admitted more than three times was 30 times higher than those patients who were admitted by three times or less [adjusted odds ratio (AOR) = 30.081; 95% confidence interval (CI) = 8.204 - 110.3; p<0.001)]. Conclusion It was found that those patients who had three times VOC episodes in our studied period are more liable to have frequent episodes in the future which might necessitate urgent intervention for these patients.

Study protocol for a randomized, blinded, controlled trial of ketamine for acute painful crisis of sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) is an inherited hematological disorder where the shape of red blood cells is altered, resulting in the destruction of red blood cells, anemia, and other complications. SCD is prevalent in the southern and eastern provinces of the Arabian peninsula. The most common complications for individuals with SCD are acute painful episodes that require several doses of intravenous opioids, making pain control for these individuals challenging. Instead of opioids, some studies have suggested that ketamine might be used for pain control in acute pain episodes of individuals with SCD. This study aims to evaluate whether the addition of ketamine to morphine can achieve better pain control, decreasing the number of repeated doses of opiates. We hypothesize that early administration of ketamine would lead to a more rapid improvement in pain score and lower opioid requirements. METHODS AND ANALYSIS: This study will be a prospective, randomized, concealed, blinded, pragmatic parallel group, controlled trial enrolling adult patients with SCD and acute vaso-occlusive crisis pain. All patients will receive standard analgesic therapy during evaluation. Patients randomized to the treatment arm will receive low-dose ketamine (0.3 mg/kg in 0.9% sodium chloride, 100 ml bag) in addition to standard intravenous hydration, while those in the control group will receive a standard dose of morphine (0.1 mg/kg in 0.9% sodium chloride, 100 ml bag) in addition to the standard intravenous hydration. All healthcare providers will be blinded to the treatment arm. Data will be analyzed according to the intention-to-treat principle. The primary outcome is improvement in pain severity using the Numerical Pain Rating Score. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03431285 . Registered on 13 February 2018.

The role of a low-dose ketamine-midazolam regimen in the management of severe painful crisis in patients with sickle cell disease.

CONTEXT: Acute pain is one of the main causes of hospital admission in sickle cell disease, with variable intensity and unpredictable onset and duration. OBJECTIVES: We studied the role of a low-dose intravenous (IV) ketamine-midazolam combination in the management of severe painful sickle cell crisis. METHODS: A retrospective analysis was performed with data from nine adult patients who were admitted to the intensive care unit with severe painful sickle cell crises not responding to high doses of IV morphine and other adjuvant analgesics. A ketamine-midazolam regimen was added to the ongoing opioids as an initial bolus of ketamine 0.25mg/kg, followed by infusion of 0.2-0.25mg/kg/h. A midazolam bolus of 1mg followed by infusion of 0.5-1mg/h was added to reduce ketamine emergence reactions. Reduction in morphine daily requirements and improvement in pain scores were the determinants of ketamine-midazolam effect. The t-tests were used for statistical analysis. RESULTS: Nine patients were assessed, with mean age of 27±11 years. Morphine requirement was significantly lower after adding the IV ketamine-midazolam regimen. The mean±SD IV morphine requirement (milligram/day) in the pre-ketamine day (D0) was 145.6±16.5, and it was 112±12.2 on Day 1 (D1) of ketamine treatment (P=0.007). The Numeric Rating Scale scores on D0 ranged from eight to ten (mean 9.1), but improved to range from five to seven (mean 5.7) on D1. There was a significant improvement in pain scores after adding ketamine-midazolam regimen (P=0.01). CONCLUSION: Low-dose ketamine-midazolam IV infusion might be effective in reducing pain and opioid requirements in patients with sickle cell disease with severe painful crisis. Further controlled studies are required to prove this effect.