Intravenous lidocaine in cancer-related neuropathic pain: case series

Introduction: Administering systemic lidocaine has been shown to deliver effective analgesia for both cancer-related and non-cancer pain. Adverse effects and toxicity are rare with controlled administration. Objective: To report the results obtained after the indication to manage with IV lidocaine infusion to control neuropathic pain flares in 9 cancer patients. Methodology: Observational, descriptive, case series-type study. A search was conducted in the files of the Pain and Palliative Care Service of the National Cancer Institute - Instituto Nacional de Cancerología - in Bogotá. Patients over 18 years old diagnosed with cancer, who experienced high intensity neuropathic pain and with the cognitive ability to rate their pain in a numerical analogue scale (NAS), without any absolute contraindications for the use of IV lidocaine were included; patients were assessed between September 27 and November 21, 2019. Results: 9 patients experiencing a pain flare-up which was characterized as neuropathic were registered, of which 89 % had some improvement following the administration of an initial lidocaine bolus. After one hour, 60 % reported over 40% improvement in the initial NAS. After 24 hours all patients had experienced some improvement, with a reduction of 46% in the pain scale as compared to the baseline. Conclusions: In this series of cases, the intravenous infusion of lidocaine as an option for the management of neuropathic pain flares seems to reduce pain intensity following the initial bolus administration.

High molecular weight hyaluronan – a potential adjuvant to fluid resuscitation in porcine abdominal sepsis

While fluid resuscitation is fundamental in the treatment of sepsis-induced tissue hypo-perfusion, a sustained positive fluid balance is associated with excess mortality. Crystalloids are the mainstay of fluid resuscitation and use of either synthetic colloids or albumin is controversial. Hyaluronan, an endogenous glycosaminoglycan with high affinity to water, has not been tested as adjuvant in fluid resuscitation. We sought to evaluate the effects of hyaluronan as an adjuvant to fluid resuscitation in peritonitis induced sepsis. In a prospective, parallel-grouped, blinded model of porcine peritonitis-sepsis, we randomized animals to intervention with adjuvant hyaluronan (add-on to standard therapy) (n=8) or 0.9% saline (n=8). After the onset of hemodynamic instability the animals received an initial bolus of 0.1 % hyaluronan 1 mg/kg/10 min or placebo (saline) followed by a continuous infusion of 0.1% hyaluronan (1 mg/kg/h) or saline during the experiment. We hypothesized that the administration of hyaluronan would reduce the volume of fluid administered (aiming at stroke volume variation <13%) and/or attenuate the inflammatory reaction. Total volumes of intravenous fluids infused were 17.5 ± 11 ml/kg/h vs. 19.0 ± 7 ml/kg/h in intervention and control groups, respectively ( p = 0.442). Plasma IL-6 increased to 2450 (1420 – 6890) pg/ml and 3700 (1410 – 11960) pg/ml (18 hours of resuscitation) in the intervention and control groups (NS). In a post-hoc analysis, modified shock index remained lower in intervention group ( p = 0.011 - 0.037). In conclusion adjuvant hyaluronan did not reduce the volume needed for fluid administration or decrease the inflammatory reaction. Adjuvant hyaluronan was, however, associated with lower modified shock index. Bearing in mind that the experiment has a limited group-size we suggest that further studies on hyaluronan in sepsis are warranted.

The Intestinal Barrier Function and Intra-Abdominal Pressure Depend on Postoperative Analgesia Technique in Children with Appendicular Peritonitis

Introduction. Peritonitis is one of the risk factors for the development of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS). The plasma citrulline and intestinal fatty acid-binding protein (I-FABP) are informative markers of intestinal barrier function. The aim of this study was to determine the correlation of the plasma citrulline and I-FABP with intra-abdominal pressure (IAP) and their relation to analgesia techniques in children suffering from appendicular peritonitis. Materials and Methods. 74 children operated for appendicular peritonitis were randomized into three groups of postoperative analgesia: “Opioids” (n = 25), intravenous morphine of 10 mcg/kg/h; “Lidocaine” (n = 23), intravenous lidocaine with initial bolus of 1.5 mg/kg and then infusion of 1.5 mg/kg/h; and “EA” (n = 26), epidurally 0.25% bupivacaine with initial bolus of 1 mg/kg and then infusion of 0.4 mg/kg/year. Retrospectively patients in each group were divided into the following subgroups: “without IAH” (n = 33), “IAH” (n = 27), and “ACS” (n = 14). We detected citrulline and I-FABP in plasma on day 1 (D1) and day 3 (D3) of hospital stay. Results. The patients without IAH on D1 presented significantly higher plasma citrulline (23.7 (16.0–31.3) nmol/ml) and lower I-FABP (76.9 (32.6–121.1) pg/ml) levels compared with patients in subgroup “IAH” (9.3 (7.3–11.3) nmol/ml and 226.0 (161.8–290.3) pg/ml, respectively) and subgroup “ACS” (6.9 (5.3–8.6) nmol/ml and 1011.7 (731.9–1291.5) pg/ml, respectively). The IAP had strong inverse correlation (rs = −0.74; p < 0.00001 ) with citrulline and positive strong correlation (rs = 0.73; p < 0.00001 ) with I-FABP. The citrulline in patients with IAH during three days postoperatively increased significantly in “Lidocaine” to 72% ( p = 0.01 ) and in “EA” to 138% ( p = 0.02 ), but it decreased to 13% ( p = 0.37 ) in “Opioids” group. In children with ACS, citrulline on D3 was significantly higher than that on D1 and increased in “Lidocaine” to 59% ( p = 0.05 ) and in “EA” to 134% ( p = 0.001 ), but in “Opioids” it decreased to 30% ( p = 0.48 ). The I-FABP in patients with IAH decreased to 12% in “Lidocaine” group ( p = 0.86 ) and to 75% in “EA” group ( p = 0.01 ), but it increased to 37% ( p = 0.57 ) in “Opioids” group. During observation period, I-FABP in patients with ACS decreased significantly in “Lidocaine” to 42% ( p = 0.05 ) and in “EA” to 96% ( p = 0.003 ), but it increased in “Opioids” to 63% ( p = 0.22 ). Conclusions. The IAP was inversely correlated with plasma citrulline and positively correlated with I-FABP in children with appendicular peritonitis. Epidural analgesia is the most protective for intestinal wall barrier function in patients at risk of IAH and ACS.

Extended Injection Intervals of Gonadotropins With Superficial Skin Administration In Ivf Treatment Is both Cost-Effective and Patient-Friendly

BackgroundWomen undergoing IVF treatments have to receive daily injections of rFSH for multiple follicles growth based on the short half-life of rFSH administered subcutaneously. This study was designed to assess if longer intervals of injection, based on rFSH half-life of 102 hours under superficial subcutaneous administration, effective for women receiving IVF.MethodsOne hundred women, aged 25–45, requesting IVF treatments from January to December 2018 were recruited in this observatory study. All women received long protocol employing GnRH-agonist since day 18 of the previous cycle. An initial bolus of 900 IU rFSH was injected into superficial subcutaneous skin at day 2 of the treatment cycle followed by longer intervals with added doses at day 7 and/or day 10. The main outcomes included the dose of gonadotropin and numbers of injection, serum FSH level, and mature oocytes retrieved.ResultsA total of 70 women completed the treatments, in which 10, 30, and 30 women received one, two and three injections of rFSH, respectively. On average, 2.31 ± 0.73 numbers of Gn injection and 1662 ± 397 IU of rFSH were administered. In comparison with baseline FSH level of 5.6 ± 2.2 IU/L, the serum concentrations of FSH were 35.3 ± 7.0 to 10.7 ± 3.7 IU/L at 1 to 5 days after an initial 900 IU rFSH administration. There were 10.5 ± 6.6 mature oocytes retrieved which resulted in 7.3 ± 5.1 two pronuclei embryos, and 1.8 ± 0.6 embryos were transferred back to the uterus and the remaining embryos were cryopreserved. In total, 72%, 91%, and 31% were noted for fertilization, cleavage, and implantation rates, respectively. The cumulative live birth rate was 36%.ConclusionsBased on the serum FSH levels detected, rFSH only needs to be administered every five days instead of daily injection. This administration mode with less injections and much less expenses for gonadotropin might reach the goal of a more patient-friendly and cost-effective treatment for IVF. Regarding higher response and efficacy of the present study, this administration mode could be employed in women with poor ovarian reserve and in women of poor or suboptimal ovarian response.Trial registration: None

Neonatal Hypernatremic Dehydration Associated with Lactation Failure

Hypernatremic dehydration secondary to lactation failure remains a potentially life-threatening condition in countries where advanced laboratory investigations are scarce. An 11-day term baby with excessive weight loss (33.6%), reduced urine output, fever, jaundice, doughy skin, opisthotonus posturing, and tachycardia with poor perfusion was presented to our neonatal care. The baby was diagnosed with shock with hypernatremic dehydration. An initial bolus of 20 ml/kg of N/S was repeated 3 times (each over 20 minutes), i.e., a total of 204 ml was given over 1 hr, until the vital signs were normalized to PR-145, RR-45, T-37.2°C, SPO2-100%, and CRT < 3 seconds, and the baby began to void urine. Free water deficit and sodium excess was managed by gradual and slow correction over 72 hours to prevent cerebral oedema and neurologic sequelae. The baby required reconstituted solutions of 5% D/W + 1/2 N/S at a rate of 27 ml/hr for 72 hrs. Sepsis and hyperbilirubinemia were treated with antibiotics and phototherapy. Management of symptomatic hypernatremic dehydration must be considered in settings with inadequate laboratory facilities.

Best-practice IgM- and IgA-enriched immunoglobulin use in patients with sepsis

Background Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Despite treatment being in line with current guidelines, mortality remains high in those with septic shock. Intravenous immunoglobulins represent a promising therapy to modulate both the pro- and anti-inflammatory processes and can contribute to the elimination of pathogens. In this context, there is evidence of the benefits of immunoglobulin M (IgM)- and immunoglobulin A (IgA)-enriched immunoglobulin therapy for sepsis. This manuscript aims to summarize current relevant data to provide expert opinions on best practice for the use of an IgM- and IgA-enriched immunoglobulin (Pentaglobin) in adult patients with sepsis. Main text Sepsis patients with hyperinflammation and patients with immunosuppression may benefit most from treatment with IgM- and IgA-enriched immunoglobulin (Pentaglobin). Patients with hyperinflammation present with phenotypes that manifest throughout the body, whilst the clinical characteristics of immunosuppression are less clear. Potential biomarkers for hyperinflammation include elevated procalcitonin, interleukin-6, endotoxin activity and C-reactive protein, although thresholds for these are not well-defined. Convenient biomarkers for identifying patients in a stage of immune-paralysis are still matter of debate, though human leukocyte antigen–antigen D related expression on monocytes, lymphocyte count and viral reactivation have been proposed. The timing of treatment is potentially more critical for treatment efficacy in patients with hyperinflammation compared with patients who are in an immunosuppressed stage. Due to the lack of evidence, definitive dosage recommendations for either population cannot be made, though we suggest that patients with hyperinflammation should receive an initial bolus at a rate of up to 0.6 mL (30 mg)/kg/h for 6 h followed by a continuous maintenance rate of 0.2 mL (10 mg)/kg/hour for ≥ 72 h (total dose ≥ 0.9 g/kg). For immunosuppressed patients, dosage is more conservative (0.2 mL [10 mg]/kg/h) for ≥ 72 h, without an initial bolus (total dose ≥ 0.72 g/kg). Conclusions Two distinct populations that may benefit most from Pentaglobin therapy are described in this review. However, further clinical evidence is required to strengthen support for the recommendations given here regarding timing, duration and dosage of treatment.

Continuous intravenous low-dose diclofenac sodium to control a central fever after ischemic stroke in the intensive care unit: a case report and review of the literature

Introduction Elevation in body temperature within the first 24 hours of ischemic stroke is fairly common and known to be associated with worse outcomes. Only after thoroughly ruling out infection and the noninfectious etiologies and in the appropriate clinical setting should the diagnosis of central fever be made. Acetaminophen and nonsteroidal anti-inflammatory drugs are typical therapeutic options. External cooling is frequently used when pharmacologic interventions are inadequate. However, reports have suggested that neurogenic fevers are somewhat resistant to traditional pharmacologic therapies. Case presentation We describe a case of a Caucasian patient with central fever after ischemic stroke not responsive to acetaminophen administration and external cooling. After an initial bolus of diclofenac sodium (0.2 mg/kg in 100 ml of saline solution for 30 minutes), a continuous infusion (75 mg in 50 ml of saline solution) was started. After 5 days of treatment, the patient’s body temperature was below 37.5 °C, and the diclofenac sodium infusion was stopped. Conclusions We observed that a low-dose diclofenac sodium infusion was effective in treating fever without systemic side effects. This treatment may be suggested as an alternative to conventional antipyretic drugs, but additional clinical trials are required.

P1860Unfractionated heparin dose and complication rate in catheter ablation of atrial fibrillation, a comparison between uninterrupted therapy with phenprocoumon and direct oral anticoagulants

Background Catheter ablation of atrial fibrillation is known for the combining risks of thromboembolism (TE) and major bleedings. This urges a better understanding and optimization of the intraprocedural anticoagulation management. Differences in unfractionated heparin (UFH) requirements and anticoagulation time (ACT) levels between patients on different uninterrupted oral anticoagulation (OAC) agents have been studied. However, the clinical relevance, in terms of periprocedural TE and bleeding events, of UFH administration according to ACT monitoring among patients on different OAC agents, needs to be addressed. Objective To evaluate how the ACT monitoring and differences in intraprocedural UFH requirements among different anticoagulant agents, may translate to clinical outcome, in terms of periprocedural incidence of thromboembolic and bleeding events. Methods We retrospectively studied 1571 cases who underwent catheter ablation for atrial fibrillation between January 2011 and May 2017. Cases were on an uninterrupted oral OAC therapy of Vitamin K Antagonists (VKA)(713), Rivaroxaban (RG)(385), Dabigatran (DG)(260), Apixaban (AG)(192) and Edoxaban (EG)(21). First ACT measurements after the initial bolus of UFH (1ehz748.0610U), mean ACT measurements, total UFH doses/kg (Body Weight)/min (duration of procedure) and incidence of major periprocedural events were compared among the above OAC groups. Results The mean ACT (sec) was significantly lower in the AG and greater in the VKA (313,7±47 vs 340,5±49, p<0,001). Significantly lower UFH doses (U/kg/min) were required to reach the target ACT in VKA compared to RG, DG, AG and EG (0,69±0,4 vs 1,41±0,76; 1,42±0,7; 1,63±0,8; 1,37±0,4 respectively, p<0,001) The proportion of patients who achieved a target ACT value within 30 minutes after the fixed first UFH Bolus of 10 000 U was significantly lower in DG and AG compared to VKA, EG and RG group (51,5% and 49% vs 53%, 71,4%, and 61,8% respectively p=0,005). The incidence of periprocedural TE events and bleedings showed no significant difference among OAC groups. However, the 22 patients with a periprocedural TE event had significantly lower UFH doses (U)/ Duration of catheter ablation (min) compared to the ones without periprocedural TE (62,71±44,5 vs 94,4±66,4, p=0,026), despite equivalent mean ACT values between these two groups. Patients with a periprocedural TE had also a significantly older Age (69,6±10 vs 64±10 p=0,01, higher CHADSVASC Score (3,64±1,76 vs 2,63±1,7 p=0,006), longer duration of procedure (188,9±79,1 vs 144,9±57 p=0,0001) and higher pre-Ablation INR values (2,2±0,6 vs 1,7±0,6 p=0,002). Conclusions The average UFH doses required to reach the target ACT were lower in VKA than in NOAC- groups. The incidence of periprocedural TE events and bleedings was equivalent among OAC groups. Patients with TE showed a lower UFH requirement compared to no-TE group, with both groups having mean ACT ≥300 sec.

P3534Optimal dosing of initial bolus of intravenous furosemide in acute heart failure: insights from REALITY-AHF

Background Although intravenous diuretics are a cornerstone in the treatment of patients with acute heart failure (AHF), optimal dosing of initial bolus of IV diuretics has not been well elucidated. Methods The initial IV bolus dose of furosemide and its association with outcomes were analyzed in 1290 AHF patients (median age, 81 years, 55% were male) derived from REALITY-AHF (Registry Focused on Very Early Presentation and Treatment in Emergency Department of Acute Heart Failure). The patients were divided into 3 groups; lower dose (lower than recommended dose, n=371), standard dose (same as recommended dose, n=807), and higher dose (higher than recommended dose, n=112) groups according to the recommended initial IV bolus furosemide dose derived from the maintenance loop diuretics dose (for those without taking oral loop diuretics or taking ≤40mg/day oral furosemide-equivalent loop diuretics, 20mg IV bolus furosemide; those on >40mg/day oral furosemide-equivalent loop diuretics, IV bolus furosemide at the same dose as oral loop diuretic dose). Outcomes were length of hospital stay, diuretic response (urine output achieved within 48 hours of admission per 40 mg furosemide-equivalent diuretics dose), and 60-day all-cause mortality. Results Median amount of first IV bolus furosemide dose were 10, 20, and 40 mg for lower, standard, and higher dose groups, respectively. After adjustment for other covariates, length of hospital stay was significantly longer by 2.6 days (p=0.018) in the lower dose group compared to the standard dose group, and there was no difference between the standard and high dose groups (p=0.221). Diuretic response within 48 hours of admission was significantly better in the lower dose group (beta coefficient: 244 mL, p=0.025) and significantly worse in the higher dose group (beta coefficient: - 1098 mL, p<0.001) compared to the standard dose group after adjustment for covariates. During 60 days of admission, 91 deaths were observed, and 60-day mortality was significantly higher in the higher dose group (HR: 2.80, 95% CI: 1.49–5.26, p=0.001), but not in the lower dose group (HR: 1.18, 95% CI: 0.67–2.08, p=0.571) compared to the standard dose group after adjustment for other prognostic factors. Conclusion Treatment with the recommended initial bolus of IV furosemide is associated with a shorter hospital stay compared to lower dose regimen and better diuretic response and better 60-day survival compared to higher dose regimen in patients with AHF. Acknowledgement/Funding This study was funded by The Cardiovascular Research Fund, Tokyo, Japan.