Infusion Volume Research Articles

Intraoperative low-dose ketamine infusion for postoperative pain relief in laparoscopic surgeries – A randomised, double blind controlled clinical trial

Abstract Background: Patients undergoing laparoscopic surgery often experience moderate-to-severe postoperative pain. The use of opioids for postoperative pain relief often results in respiratory depression and other adverse effects. Hence, we studied the effect of ketamine infusion administered at a low dose intraoperatively on postoperative pain relief. Materials and Methods: Fifty-two patients belonging to American Society of Anesthesia (ASA) I/ASA II, scheduled for laparoscopic surgery were randomized into two groups (n = 26). Group A received 0.2 mg/kg bolus of ketamine before the skin incision followed by an infusion of 0.1 mg/kg/h throughout the period of surgery. Group B received an equal volume of saline bolus and infusion. Postoperative pain was assessed (Numerical Rating Scale [NRS] scale) every 30 min till 6 h. The time taken for first rescue analgesia, the total amount of opioid used, and degree of sedation postoperatively were also compared. Pain scores between the groups were compared using the Chi-square test. Results: Pain scores (NRS scores) over various time intervals postoperatively were significantly reduced in the ketamine group (P < 0.001). The overall cumulative opioid consumption was significantly lower in the ketamine group compared to the placebo (69.29 ± 23.35 mg vs. 107.88 ± 35.21 mg, respectively, P = 0.008). There was also a significant difference in time to first rescue analgesia between the ketamine and placebo groups (2.60 ± 1.87 h vs. 0.43 ± 0.85 h, respectively, P = 0.001). Conclusion: Intraoperative low-dose ketamine infusion as an adjuvant significantly decreased postoperative pain with a reduced total dose of opioid consumption and a delayed time to first rescue analgesic.

Incidence of Hemidiaphragmatic Paralysis After Ultrasound Guided Low Dose Interscalene Brachial Plexus Block

Background and Aims: Hemidiaphragmatic paralysis is a complication of single shot and continuous interscalene brachial plexus block that can be minimised by ultrasound guided extra fascial catheter placements and by limiting the amount of local anaesthetic administered. In this study, we report incidence of hemidiaphragmatic paralysis with patient-controlled infusion of low volume of ropivacaine after ultrasound guided low dose interscalene brachial plexus block (LD-ISB). Methods: Patients aged 18-65 years undergoing surgery for shoulder dislocation or proximal humerus fracture were recruited and administered general anaesthesia. Before extubation ultrasound guided LD-ISB (10 ml of 0.5% ropivacaine) was administered and a catheter tunneled so that patient controlled interscalene analgesia (PCIA) could be given with low volume ropivacaine. PCIA was initiated after four hours in the post operative recovery to deliver background infusion of 2 ml/h, bolus of 5ml (0.2% of ropivacaine) with lockout interval of 30 minutes for a total duration of 24 hours. Incidence of hemidiaphragmatic paralysis was recorded at extubation using M-mode ultrasonography. Before start of PCIA i.e. at 4 hours and after start of PCIA i.e. 6,12 and 24 h after extubation. Results: PCIA after LD-ISB was administered to 29 patients. Subsequently, two patients were excluded due to catheter dislodgement. The incidence of complete and partial paresis of diaphragm after extubation was 85% and 3.7% with LD-ISB respectively but was resolved before start of PCIA i.e., at 4 hours. Thus, at time of commencement of PCIA all patients had normal diaphragmatic excursions and subsequently at 6,12 and 24 h no paresis/paralysis was reported in patients administered only the background infusion or an additional single bolus dose of ropivacaine with the background infusion. Partial paresis was noted in all patients in which two bolus doses/h were administered. All patients with paresis had diaphragmatic excursion normalised in the next recording made at 4 hours and no complication was reported in any patient. VAS (Visual Analog Scale) was below 3 at all time points. Conclusion: Partial/complete paresis after a single shot injection of 10 ml of 0.5% ropivacaine resolves in 4 hours. PCIA initiated after it for subsequent 20 hours with a single bolus dose of 5ml of 0.2% ropivacaine and background infusion at 2 ml/h does not cause phrenic paresis. Partial paresis is reported with two bolus doses/h, but it is clinically asymptomatic. Thus, the above dose regimes are safe and effective in managing post-operative pain. Keywords: Interscalene block, Diaphragmatic paresis, Ropivacaine, continuous infusion, Analgesic efficacy

Machine learning-based identification of the risk factors for postoperative nausea and vomiting in adults.

Postoperative nausea and vomiting (PONV) is a common adverse effect of anesthesia. Identifying risk factors for PONV is crucial because it is associated with a longer stay in the post-anesthesia care unit, readmissions, and perioperative costs. This retrospective study used artificial intelligence to analyze data of 37,548 adult patients (aged ≥20 years) who underwent surgery under general anesthesia at Tohoku University Hospital from January 1, 2010 to December 31, 2019. To evaluate PONV, patients who experienced nausea and/or vomiting or used antiemetics within 24 hours after surgery were extracted from postoperative medical and nursing records. We create a model that predicts probability of PONV using the gradient tree boosting model, which is a widely used machine learning algorithm in many applications due to its efficiency and accuracy. The model implementation used the LightGBM framework. Data were available for 33,676 patients. Total blood loss was identified as the strongest contributor to PONV, followed by sex, total infusion volume, and patient's age. Other identified risk factors were duration of surgery (60-400 min), no blood transfusion, use of desflurane for maintenance of anesthesia, laparoscopic surgery, lateral positioning during surgery, propofol not used for maintenance of anesthesia, and epidural anesthesia at the lumbar level. The duration of anesthesia and the use of either sevoflurane or fentanyl were not identified as risk factors for PONV. We used artificial intelligence to evaluate the extent to which risk factors for PONV contribute to the development of PONV. Intraoperative total blood loss was identified as the potential risk factor most strongly associated with PONV, although it may correlate with duration of surgery, and insufficient circulating blood volume. The use of sevoflurane and fentanyl and the anesthesia time were not identified as risk factors for PONV in this study.

Preventing Fluid Retention After Subarachnoid Haemorrhage During Administration of Endothelin Receptor Antagonist.

Prevention of delayed cerebral infarction (DCI) due to cerebral vasospasm after subarachnoid haemorrhage (SAH) has been done with intravenous Rho kinase inhibitors (ROCKI), ozagrel sodium (TXA2I), selective ROCKI infusion (ROCKI i.a.), and cerebrospinal fluid (CSF) drainage. The endothelin receptor antagonist (ERA, clazosentan) became available in 2022 and is said to be highly recommended for DCI prevention, while fluid retention such as pleural effusion and pulmonary oedema accumulation is often experienced. We investigated the relationship between patient background, fluid retention, and ERA. Ten consecutive SAH patients treated with ERA from July to December 2022 were included. We examined the results of blood sampling on admission, echocardiography, chest computed tomography (CT), with postoperative DCI, and hydrocephalus requiring cerebrospinal fluid shunt (hydro), and symptomatic fluid retention requiring albumin and furosemide (third fluid space). Two males and eight females, mean age 63years, mean preoperative World Federation Neurosurgical Surgeons (WFNS) grade 3.5, mean creatinine 0.94, mean brain natriuretic peptide (NT-proBNP). In 1883, two patients with Takotsubo cardiomyopathy and four patients with neurogenic pulmonary oedema are present. All patients underwent coil embolisation, and postoperative CSF drainage, ROCKI, TXA2I systemic administration, and ROCKI i.a. There were one DCI, three hydro, and five third fluid cases. Concerning the third fluid, the only significant difference was found in the age. An improvement in fluid retention after ERA discontinuation in old patients was shown. Our experience suggests that age may be the most influential factor. Based on these results, we have also found that by avoiding the use of ERA in patients older than 80years, strictly limiting the infusion volume when using ERA, and actively using the drugs for heart failure early on, the frequency of suffering from third fluid space is reduced.

Comparative evaluation of the perioperative anesthesia methods for cancer patients undergoing pancreaticoduodenectomy

BACKGROUND: Pancreatoduodenal resections are one of the most traumatic and technically complex interventions in abdominal surgery. The correct anesthetic management and pain relief allow to substantially reduce the risk of perioperative complications, which remains high even in high-volume oncology centers with extensive experience. Finding new components and methods of anesthesia combined with evaluation of their effectiveness and safety remains a pressing issue.
 AIM: To evaluate the efficacy and safety of using intravenous lidocaine infusion as a component of anesthesia and postoperative analgesia in cancer patients during pancreatoduodenal resection.
 MATERIALS AND METHODS: We analyzed the course of anesthesia, operation and postoperative period of 43 patients (mean age 63.2±7.1 years) undergoing pancreaticoduodenectomy. For the purposes of the study, patients were randomly divided into 2 groups, based on anesthesia method: for the first group (n=19) we used epidural analgesia as a component of perioperative anesthesia, for the second group (n=24) we used prolonged intravenous infusion of lidocaine at an average dose of 1 mg/(kg×h). We analyzed the severity of pain syndrome according to Numeric rating scale for pain in postoperative period, as well as opioid requirement, the time of gastrointestinal function recovery, and post-operative complications frequency. In order to prevent systemic toxicity, drug monitoring was carried out — the determination of the plasma concentration of lidocaine.
 RESULTS: Perioperative opioid requirement was comparable between groups, with no statistically significant differences observed. The degree of pain syndrome according to the Numeric rating scale for pain did not differ statistically, except for the number of points during activation on day 3: 4.00 (95% confidence interval 3.49–4.51) for epidural analgesia group, compared to 3.12 (95% confidence interval 2.64–3.61) for lidocaine infusion group, p=0.014. There was also a statistically significant increase in infusion volume for epidural analgesia group compared to lidocaine infusion group [8.83 ml/(kg×h) (Q1=7.90; Q3=10.06) and 7.33 ml/(kg×h) (Q1=6.28–Q3=8.49) respectively, p=0.034], as well as a greater need for intraoperative vasopressor support among the patients [15 (78.9%) and 10 (43.5%) respectively, p=0.029]. In the lidocaine group, the time to onset of peristalsis was significantly shorter than in the epidural analgesia group [median 48.0 h (Q1=48.00; Q3=72.00) compared to median 60.0 h (Q1=36.00; Q3=64.50) respectively, p=0.042]. The frequency of postoperative complications did not differ between the groups.
 CONCLUSION: Based on a comparative analysis of the study results, it can be concluded that prolonged intravenous infusion of lidocaine, as a component of perioperative anesthetic protection during pancreatoduodenal resections, is safe and comparable in terms of analgesic efficacy to epidural blockade.

A Phase 1 Open-Label Study to Assess the Tolerability, Safety, and Immunogenicity of Hyaluronidase-Facilitated Subcutaneous Immunoglobulin 20% in Healthy Adults

PurposeHyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) 20% will allow reduced infusion volumes and frequency versus existing subcutaneous therapies such as fSCIG 10% and conventional subcutaneous immunoglobulin 20%, respectively. We assessed the tolerability, safety, and immunogenicity of warmed and unwarmed fSCIG 20%.MethodsThis phase 1, single-dose, open-label, three-arm study enrolled healthy adults aged 19–50 years (inclusive) at a single US center (NCT05059977). Post-screening, participants received a single fSCIG 20% dose comprising recombinant human hyaluronidase and varying doses of in-line warmed or unwarmed immunoglobulin G (IgG) during a 4-day treatment period in a sentinel and sequential dosing design (treatment arm 1, warmed IgG 20% 0.4 g/kg; treatment arm 2, warmed IgG 20% 1.0 g/kg; treatment arm 3, unwarmed IgG 20% 1.0 g/kg). Participants were followed for 12 (± 1) weeks post-infusion. The primary endpoint was tolerability (“tolerable” infusions were not interrupted, stopped, or reduced in rate owing to fSCIG 20%-related treatment-emergent adverse events (TEAEs)). Secondary endpoints included occurrence of TEAEs.ResultsOverall, 24 participants were included, 8 per treatment arm (mean age 39.0 years, 54.2% men). All participants tolerated the infusions. All TEAEs were mild (107 events, in all participants), and all participants experienced fSCIG 20%-related (105 events) and local (102 events) TEAEs. Infusion site erythema and infusion site swelling were most frequently reported. No serious TEAEs occurred, and no participants discontinued the study owing to TEAEs.ConclusionfSCIG 20% was well-tolerated with a favorable safety profile in healthy adults. Future studies will evaluate fSCIG 20% in primary immunodeficiency diseases.Trial registration number (ClinicalTrials.gov): NCT05059977 (registered 28 September 2021).

Impact of strict fluid management on the treatment outcome of clazosentan for cerebral vasospasm

ObjectiveClazosentan (CLA) reduces cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH). However, adverse events including pulmonary edema were reported. We examined whether the strict management of fluid balance reduces the adverse events and improves patient outcomes. MethodsPatients with aSAH between 2020 and 2023 were included. They were divided into pre-CLA (before CLA approval) and post-CLA (after approval) groups. The patients in the post-CLA group were further divided into the post-CLA1 (before the change in fluid management) and post-CLA2 (after the change) groups. To achieve fluid balance of 0–500 ml/day according to the modified protocol, the infusion volume was restricted. ResultsThe daily fluid balance increased from the pre-CLA to the post-CLA1 periods (p = 0.01). The protocol changes decreased the pulmonary edema (post-CLA1 vs. post-CLA2, 44 vs. 22 %, p = 0.09) and discontinuation of CLA (44 vs. 9 %, p < 0.01). The incidence of symptomatic spasm (SS) and delayed cerebral infarction (DCI) in the post-CLA2 were slightly reduced without significant differences (SS: 17 vs. 13 %, p = 0.69; DCI: 11 vs. 9 %, p = 1.00). ConclusionStrict management of fluid balance during CLA treatment reduced the adverse events and discontinuation of CLA administration. Fluid restriction may positively affect the management of cerebral vasospasms.

Efficacy of intravenous magnesium sulfate infusion on postoperative pain and quality of recovery for septorhinoplasty: a randomized controlled study

Background The pain that occurs after septorhinoplasty is an important factor affecting the comfort of the patient. Objectives To investigate the effect of perioperative intravenous magnesium sulfate infusion on postoperative pain and quality of recovery in patients underwent septorhinoplasty surgery. Material and methods One hundred twenty patients who underwent septorhinoplasty were randomly divided into two groups. Magnesium group received intravenous magnesium after induction of anesthesia (30 mg/kg), then infused until the end of the surgical procedure (9 mg/kg). The placebo group received the same volume of saline infusion. The VAS score was used for postoperative pain assessment, and the Quality of Recovery-40 (QoR-40) score was used for the assessment of recovery status. Results The postoperative 30 min, 1st, 2nd, 4th (p < .001) and 24th hour (p < .05) VAS scores of the patients in the magnesium infusion group were significantly lower compared to the placebo group. Also; in terms of physical comfort (p < .001), emotional state (p < .05), psychological support, pain and total score values (p < .001), patients in magnesium group had significantly higher QoR-40 scores than those in placebo group. Conclusion Intraoperative magnesium infusion, which is widely used in many surgeries to provide controlled hypotension, also contributes significantly to patient comfort with its positive effect on postoperative pain and recovery scores.

Exploring Coagulation and Fibrinolysis Activation As Mechanisms of Sepsis-Related Tissue Damage in Patients with Severe Neutropenia and Thrombocytopenia Secondary to Hematological Malignancies

Sepsis is a life-threatening end-organ dysfunction resulting from dysregulated host responses to infection with physiopathology not fully understood. Yet, it has been long recognized that platelets and neutrophil extracellular traps collaborate to promote secondary tissue damage. Interestingly, patients with hematological malignancies and febrile neutropenia (FN) secondary to chemotherapy, with neutrophils and platelet counts frequently around zero, develop sepsis and septic shock, raising questions about which mechanisms are involved. Here, we show that extracellular vesicles (EVs) and activation of the fibrinolytic system are two potential mediators of tissue damage in sepsis among patients with very low platelets and neutrophil counts. The study population consisted of patients with hematologic malignancies who underwent antineoplastic treatment and that presented neutrophil counts &amp;lt; 500/μl and temperature ≥ 37.5 °C. Sepsis was defined as an increase of at least 2 points in the Sequential Organ Failure Assessment (SOFA) score and septic shock was defined by the need for vasoactive drugs after adequate volume infusion. Samples were obtained after FN diagnosis, at sepsis onset, and 72 h thereafter. A control group of patients with hematological malignancies and chemotherapy-induced neutropenia without fever was also included. Forty-two subjects, both genders, aged from 21 to 71 years were included and categorized into 4 groups, referred to: FN (n=18), FN + sepsis (n=10), FN + sepsis 72h (n=9), and the control group (n=18). The clinical and laboratory characteristics of these groups are described in Table 1. We first evaluated whether the release of EVs could be associated with the development of sepsis in these patients. EVs were characterized and enumerated from platelet-poor plasma (PPP) obtained from all groups and then separated through high-speed centrifugation (30 min, 20,000 g, 4ºC). EVs were marked with CD146 and 144 for endothelial cells; CD66b for granulocytes; CD14 and CD68 for monocytes, CD41 for platelets, and CD142 for tissue factor (TF) expression. Lactadherin and calcein were used to identify EVs according to size and integrity. Samples were acquired in a flow cytometer, Cytoflex S, with 30 μL/min flow rate and calibration microbeads were used to identify EV of specific sizes (Rosetta). The main findings are shown in Table 2. The main results were an increase in monocyte-derived EVs in patients with FN after sepsis onset (FN + sepsis 72h), compared to all other groups (p=0.01). Moreover, the expression of TF + was higher in these EVs (FN + sepsis 72h) when compared to EVs obtained at sepsis onset (FN + sepsis): 0.50 (IQR 0.29 - 1.10) events/μL versus 0.28 (IQR 0.12 - 0.56) in FN + Sepsis (p=0.03). Additionally, an increase in endothelial (CD146 +) and granulocyte-derived EVs were observed at the same time-point compared to FN and the control group. Of note, monocyte-derived EVs counts were not correlated with monocyte cell counts (Rs= 0.03; p=0.94). Given that coagulation activation plays a role in the immunothrombotic cascade known to mediate tissue damage in sepsis, we also explored whether thrombin and plasmin generation were increased in these patients. Briefly, the assay used PPP and two independent fluorometric substrates for thrombin (Boc-Val-Pro-Arg-MCA) and plasmin (Boc-Glu-Lys-Lys-MCA) in a 96-well plate, lately initiated by the addition of TF (10 pM). The plate was read in a fluorometric spectrophotometer for 4 h. Results are shown in Table 2, and no differences were observed in thrombin generation. However, the area under the curve of plasmin generation, which could be interpreted as a proxy of the plasma fibrinolytic potential, was lower in both FN + sepsis and FN + sepsis 72 h when compared to FN and the control group. Our findings reveal that EVs might present a role in the pathogenesis of sepsis in a scenario where cells known to be critical to this process are virtually absent. The increase of TF + EVs from monocytes, which has been demonstrated in classical sepsis, seems to be relevant even in this context, warranting additional studies using functional assays to further explore this mechanism of tissue damage. Our results also demonstrate that hypofibrinolysis is a characteristic of FN-associated sepsis, suggesting that deregulation of the fibrinolytic system is at least in part independent of the participation of granulocytes and platelets in these patients.

Effect of anesthesia induction with butorphanol on postoperative nausea and vomiting: A randomized controlled trial

BACKGROUND Postoperative nausea and vomiting (PONV) are common complications that affect the recovery and well-being of elderly patients undergoing gastrointestinal laparoscopic surgery. AIM To investigate the effect of butorphanol on PONV in this patient population. METHODS A total of 110 elderly patients (≥ 65 years old) who underwent gastrointestinal laparoscopic surgery were randomly assigned to receive butorphanol (40 μg/kg) or sufentanil (0.3 μg/kg) during anesthesia induction in a 1:1 ratio. The measured outcomes included the incidence of PONV at 48 h after surgery, intraoperative dose of propofol and remifentanil, Bruggrmann Comfort Scale score in the postanesthesia care unit (PACU), number of compressions for postoperative patient-controlled intravenous analgesia (PCIA), and time to first flatulence after surgery. RESULTS The results revealed a noteworthy reduction in the occurrence of PONV at 24 h after surgery in the butorphanol group, when compared to the sufentanil group (T1: 23.64% vs 5.45%, T2: 43.64% vs 20.00%, P &lt; 0.05). However, no significant variations were observed between the two groups, in terms of the clinical characteristics, such as the PONV or motion sickness history, intraoperative and postoperative 48-h total infusion volume and hemodynamic parameters, intraoperative dose of propofol and remifentanil, number of postoperative PCIA compressions, time until the first occurrence of postoperative flatulence, and incidence of PONV at 48 h post-surgery (all, P &gt; 0.05). Furthermore, patients in the butorphanol group were more comfortable, when compared to patients in the sufentanil group in the PACU. CONCLUSION The present study revealed that butorphanol can be an efficacious substitute for sufentanil during anesthesia induction to diminish PONV within 24 h following gastrointestinal laparoscopic surgery in the elderly, simultaneously improving patient comfort in the PACU.

Infusion therapy in critical patients (state of problem). Part 1

Infusion therapy is an important component of many diseases treatment – and one of the main methods of intensive care for intensive care patients. Active infusion therapy using different infusion media, large volumes and high rates of intravenous fluid is especially relevant in critical patients, the most severe of which remains patients with septic shock. For more than two centuries of clinical use, infusion therapy has gone through a long evolutionary path and has become more effective and safer. However, like any drug, infusion therapy (in general and specific infusion media) has a number of side effects, especially when used excessively. Therefore, in recent years, the use of infusion therapy is considered as the appointment of any drug, taking into account indications, contraindications, methods of administration, dosing, duration, deescalation. This made it possible to identify the main stages of infusion therapy of critical conditions and shock: intensive infusion therapy (rapid administration of a large fluid volume), optimization of infusion therapy (reduction of the rate and volume of infusion), stabilization of the patient and minimization of infusion, de-resuscitation – removal of excess fluid from the body. With the development of clinical pathophysiology, the basic concepts of maintaining fluid homeostasis of the body in normal and critical conditions were revised, and the negative effects of infusion therapy at all stages of its use were studied. Therefore, in the intensive care of shock, the main clinical questions are: when to start fluid therapy, when to stop active fluid therapy, when to start fluid removal from the body, and when to stop fluid de-resuscitation. Thus, in order to implement the principle of personalized treatment, it is important to determine not only the «tolerance» of infusion therapy, but also the «sensitivity» to the infusion of a particular patient – the ability to maintain hemodynamics without the risk of fluid overload. Evaluation of routine clinical, instrumental and laboratory indicators of the state of macro- and microcirculation does not provide an opportunity to accurately answer these questions. Modern sonographic methods for monitoring central and peripheral cardiohemodynamics, ‘venous excess’ using Doppler and extended focus echocardiography allow us to assess the ‘tolerance of infusion therapy’. The implementation of this new direction will increase the efficiency and safety of infusion therapy and improve the outcomes of the critically ill patients’ treatment.

CTNI-28. FINAL RESULTS OF A PILOT STUDY TO EVALUATE INFUSION RATE ESCALATION TO MAXIMIZE VOLUME OF DISTRIBUTION DURING CONVECTION ENHANCED DELIVERY TO CONTRAST-ENHANCING GLIOBLASTOMA

Abstract BACKGROUND Volume of distribution (Vd) during convection enhanced delivery is impacted by the characteristics of the tissue being treated. For Glioblastoma (GBM), Vd is substantially higher in non-contrast enhancing tumor than in contrast enhancing tumor due to higher infusate efflux in enhancing tumor. We hypothesized that increasing the infusion rate could overcome the infusate efflux rate in enhancing tumor to improve the Vd to volume of infusion (Vi) ratio and provide better tumor coverage. METHODS A single center, IRB-approved pilot study was conducted under an IND (held by MAV) to perform rate escalated delivery of Topotecan with Gadolinium-DTPA to contrast-enhancing recurrent GBM (rGBM). A single Cleveland Multiport Catheter was surgically placed into enhancing tumor and then a 4-hour infusion was performed with real-time MRI visualization. Intra- and inter-patient rate escalation was performed. RESULTS 3 patients with rGBM were enrolled and treated. The initial infusion rate for patient 1 was 5 microliters/minute per microcatheter (4 total) and the final infusion rate for the third patient was 20 microliters/minute per microcatheter. We observed partial backflow at this rate and so did not escalate higher. There was coverage of both enhancing and non-enhancing tumor in all cases, and the Vd/Vi ratio ranged from 0.7 to 1.3. Patients tolerated the treatments well; there were no CTCAE Grade 3 or higher treatment related adverse events. CONCLUSIONS The higher efflux rate associate with contrast-enhancing tumor tissue can be overcome with sufficient infusion rate escalation.

DDEL-01. UTILIZING SENSOR ARRAYS FOR INTRACRANIAL PRESSURE (ICP) RESPONSE TO CEREBROSPINAL FLUID (CSF) DRUG ADMINISTRATION, AND POTENTIAL IMPLICATIONS FOR PERSONALIZED CARE IN CNS METASTASES PATIENTS

Abstract BACKGROUND Patients with leptomeningeal carcinomatosis (LC) may have elevated intracranial pressure (ICP) due to LC cancer cells having the potential to obstruct the arachnoid granulations.,Given that LC treatment may involve intrathecal (IT) drug delivery, monitoring ICP may be important for safe IT drug delivery. The EnClear device is a novel CNS drug delivery device with both intracranial and intralumbar CSF access and single-use sensing arrays that measure ICP in these dual locations. METHODS This is a non-human primate (NHP) study on three healthy NHP subjects undergoing IT gene therapy via intracerebroventricular (ICV). The sensor arrays measured ICP before, during, and after ICV infusion in both intracranial and lumbar locations. Our goal was to compare individual subject pressure response to drug administration as well as to compare lumbar and cranial pressure waveforms for concordance. Pressure response was quantified as change in pressure (ΔP) following volume (ΔV) administration, known as intracranial elastance (ΔP/ΔV). RESULTS Significant correlations were observed between ventricular and lumbar ICP waveforms with an average of 0.88 correlation coefficient. Pressure measurements between subjects demonstrated variable response to identical infusion volumes, with maximum pressures ranging from 20 mmHg to 40 mmHg. Intracranial elastance was calculated for each subject during infusions and resulted in a range of 12 to 36 mmHg/mL, a 3-fold difference in elastance between subjects. CONCLUSION In healthy NHPs, changes to cranial volume and pressure response can be measured in the lumbar space with good correlation between the two measurement locations. Despite this consistency between these two locations on the same subject, intersubject variability was seen despite identical drug administration. Pressure waveform sensing systems can be incorporated in the future to enable clinicians to understand individual patient brain compliance and leverage this knowledge for personalized drug delivery, particularly in patients with LC.

Near-Infrared Spectroscopy Monitoring to Detect Changes in Cerebral and Renal Perfusion During Hypovolemic Shock, Volume Resuscitation, and Vasoconstriction.

Rapidly changing hemodynamic conditions, such as uncontrolled hemorrhage and the resulting hypovolemic shock, are a common contributor to active duty military deaths. These conditions can cause cerebral desaturation, and outcomes may improve when regional cerebral oxygen saturation (CrSO2) is monitored using near-infrared spectroscopy (NIRS) and desaturation episodes are recognized and reversed. The purpose of this porcine study was to investigate the ability of NIRS monitoring to detect changes in regional cerebral and regional renal perfusion during hypovolemia, resuscitation by volume infusion, and vasoconstriction. Hemorrhagic shock was induced by removing blood through a central venous catheter until mean arterial pressure (MAP) was <40 mmHg. Each blood removal step was followed by a 10-minute stabilization period, during which cardiac output, blood pressure, central venous pressure, blood oxygen saturation, and CrSO2 and regional renal oxygen saturation (RrSO2) were measured. Shock was reversed using blood infusion and vasoconstriction separately until MAP returned to normal. Statistical comparisons between groups were performed using the paired t-test or the Wilcoxon signed-rank test. Using volume resuscitation, both CrSO2 and RrSO2 returned to normal levels after hypovolemia. Blood pressure management with phenylephrine returned CrSO2 levels to normal, but RrSO2 levels remained significantly lower compared to the pre-hemorrhage values (P < .0001). Comparison of the percent CrSO2 as a function of MAP showed that CrSO2 levels approach baseline when a normal MAP is reached during volume resuscitation. In contrast, a significantly higher MAP was required to return to baseline CrSO2 during blood pressure management with phenylephrine (P < .0001). Evaluation of carotid blood flow and CrSO2 indicated that during induction of hypovolemia, the two measures are strongly correlated. In contrast, there was limited correlation between carotid blood flow and CrSO2 during blood infusion. This study demonstrated that it is possible to restore CrSO2 by manipulating MAP with vasoconstriction, even in profound hypotension. However, MAP manipulation may result in unintended consequences for other organs, such as the kidney, if the tissue is not reoxygenated sufficiently. The clinical implications of these results and how best to respond to hypovolemia in the pre-hospital and hospital settings should be elucidated by additional studies.

Real-World Usage of Hyaluronidase-Facilitated Subcutaneous Immunoglobulin 10% in Patients with Multiple Myeloma Diagnosed with Secondary Immunodeficiency Disease

Introduction: In patients with mature B-cell malignancies such as multiple myeloma (MM), both the underlying disease and immunosuppressive therapy can result in patients developing secondary immunodeficiency disease (SID). SID often manifests in severe, recurrent, or persistent infections that can impair a patient's quality of life and are a major cause of morbidity and mortality in patients with MM, thereby resulting in significant clinical and socioeconomic burden. The use of immunoglobulin (Ig) replacement therapy is well established for the treatment of hypogammaglobulinemia in patients with primary immunodeficiency disease (PIDD). Hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) 10% is a dual-vial unit of IgG 10% and recombinant human hyaluronidase (rHuPH20). fSCIG 10% is approved in the USA for the treatment of adults and children aged 2 years or older with PIDD, and in the EU for adults and children of any age with PIDD or SID. fSCIG 10% is not fully integrated into standard of care for patients with SID in many countries, in part owing to comparatively less familiarity of hematologists and oncologists with the evidence supporting the use of fSCIG 10% than for intravenous IgG therapy in patients with SID. Therefore, the HyMMy study (NCT05879757) aims to generate real-world evidence to gain a better understanding of patterns of fSCIG 10% use and outcomes in patients with MM and SID. Methods: HyMMy is a prospective, noninterventional, observational study that will be conducted at 30 centers in Europe and South America. It is planned for 100 patients to be enrolled and observed over a 12-month follow-up period. The overall duration of the study will be 38 months. Patients will be eligible for inclusion if they are aged 18 years or older, have a diagnosis of MM, and fulfill the diagnosis criteria for SID: patient suffers from severe, recurrent, or persistent infection despite appropriate anti-infective treatment, and has proven specific antibody failure or a serum IgG trough level of less than 4 g/L (excluding paraprotein). Patients may enter the study after being diagnosed with SID and no more than 30 days after fSCIG 10% treatment initiation, or with no more than 2 doses of fSCIG 10% already infused ( Figure). Patients newly starting fSCIG 10% have a 30-day window from enrollment to inclusion. Patients will be excluded if they have PIDD, have received Ig treatment or prophylaxis within 3 months of enrollment, have an ongoing serious infection requiring intravenous antimicrobial therapy, have a history of malignancy other than MM within 3 years of enrollment, or have had major surgery within 2 weeks of enrollment. The primary endpoint is to characterize the real-world infusion parameters of fSCIG 10% administration (dosing and administration characteristics; treatment interval; infusion volume, sites, rate, and duration; training visits; and fSCIG 10% discontinuation, interruption, or switch to other treatment). Secondary endpoints will examine the disease course and clinical management of MM (including overall survival and healthcare resource utilization) in patients treated with fSCIG 10%. The exploratory endpoints include: burden of infection; infection rate, type, duration, and severity; patient-reported outcomes pertaining to health-related quality of life, collected via questionnaire at the patients' visit; and overall physician assessment of fSCIG 10% utilization, tolerability, and effectiveness, as measured by a 5-point Likert scale questionnaire. Results: Patient recruitment started in June 2023. Interim analysis is planned after enrollment of the first 50 patients, and the estimated end of the study is 2026. Conclusions: HyMMy is the first prospective, observational study that focuses on the assessment of fSCIG 10% utilization patterns in adults with MM diagnosed with SID. The study will help to improve understanding of the treatment patterns and options available for patients with SID and hematologic malignancies, in particular MM. Takeda Development Center Americas, Inc. funded this study. Takeda Pharmaceuticals International AG funded writing support.

Nadir Hemoglobin Concentration After Spinal Tumor Surgery: Association With Risk of Composite Adverse Events.

Retrospective case-control study. To explore the association of early postoperative nadir hemoglobin with risk of a composite outcome of anemia-related and other adverse events. We retrospectively analyzed data from spinal tumor patients who received intraoperative blood transfusion between September 1, 2013 and December 31, 2020. Uni- and multivariate logistic regression was used to explore relationships of clinicodemographic and surgical factors with risk of composite in-hospital adverse events, including death. Subgroup analysis explored the relationship between early postoperative nadir hemoglobin and composite adverse events. Among the 345 patients, 331 (95.9%) experienced early postoperative anemia and 69 (20%) experienced postoperative composite adverse events. Multivariate logistic regression analysis showed that postoperative nadir Hb (OR = .818, 95% CI: .672-.995, P = .044), ASA ≥3 (OR = 2.007, 95% CI: 1.086-3.707, P = .026), intraoperative RBC infusion volume (OR = 1.133, 95% CI: 1.009-1.272, P = .035), abnormal hypertension (OR = 2.199, 95% CI: 1.085-4.457, P = .029) were correlated with composite adverse events. The lumbar spinal tumor was associated with composite adverse events with a decreased odds compared to thoracic spinal tumors (OR = .444, 95% CI: .226-.876, P = .019). Compared to patients with postoperative nadir hemoglobin ≥11.0g/dL, those with nadir <9.0g/dL were at significantly higher risk of postoperative composite adverse events (OR = 2.709, 95% CI: 1.087-6.754, P = .032). Nadir hemoglobin <9.0g/dL after spinal tumor surgery is associated with greater risk of postoperative composite adverse events in patients who receive intraoperative blood transfusion.

Reducing time toxicity: Impact of a fast-track infusion pathway on overall wait-times and patient satisfaction at a large safety-net health system.

386 Background: Time toxicity is an emerging concept focusing on the impact of cancer care beyond traditionally measured outcomes: the time spent towards receiving care. Although the inherent complexity of cancer care can pose a challenge to improve time toxicity, addressing system and workflow inefficiencies through process improvement is an effective mitigation strategy. Here we present the impact of a fast-track infusion pathway on the wait-times and patient satisfaction at a large safety-net system. Methods: Parkland Health (PH) is the safety-net system for Dallas County, TX. The PH oncology infusion center supports cancer disciplines and other subspecialties. Factors such as timely patient arrivals, preference for coupled visits and same-day lab draws, and heterogeneity of treatments (medicine specialties vs. oncology) significantly impact wait times. In July 2022, a multidisciplinary team was formed to reduce wait times at the infusion center, including members who had previously participated in the ASCO Quality Training Program (QTP). This report is focused on developing a fast-track pathway for patients with injections or &lt;30-minute infusions. Patients with coupled appointments and same-day lab draws were eligible for fast-track. Wait times were calculated from the time patients were checked in at the front desk to the first medication administered. A dedicated team (RN and MA) and separate waiting areas/infusion bays were designated for fast-track patients. Fast-track patients were surveyed for satisfaction. Results: Baseline infusion volume for the 3 months prior to fast-track implementation was 106 patients per day with average wait time of 167 minutes. In the seven-month period after fast-track implementation, average daily fast-track and main infusion center combined volume was 115. The first PDSA cycle was focused on improving workflows and communication with pharmacy. In the second PDSA cycle, the fast-track infusions were moved to another area to infusion chairs to better patient flow. In May 2023, average volumes and wait times for fast-track and main infusion were 28/80 minutes and 87/107 minutes, respectively. This represents a 40% decrease in wait time for fast-track and 36% for main infusion. In our survey, 89% of fast-track patients reported their wait time to be shorter and 92% rated their experience good or excellent. Conclusions: Implementing and optimizing a separate process for short treatments reduced the wait times for both the short infusions (fast-track) as well as long infusions (main infusion) without a need for additional staff, infusion chairs, or space. The observed decrease in main infusion wait-time is likely the result of decongestion of their process by moving some of the volume to fast-track. We hope to further decrease our wait-times through additional PDSA cycles and leveraging process improvement methodology.

Lumbar fusion through the anterolateral mini-approach: comparison of anterior interbody (OLIF-AF) and percutaneous pedicle (OLIF-PF) fixations in the surgical treatment of single-level stenosis

Objective. To perform comparative analysis of the clinical efficacy and safety of indirect decompression of the spinal roots and interbody fusion through the lateral pre-psoas approach (OLIF) with anterolateral (OLIF-AF) and posterior percutaneous (OLIF-PF) screw fixations in the surgical treatment of single-segment lumbar stenosis.Material and Methods. A retrospective comparative analysis of treatment of 88 patients aged 29 to 72 years with single-level lumbar stenosis was carried out. Posterior instrumental fixation (OLIF-PF) was performed in 60 cases, and anterolateral (OLIF-AF) – in 28.Results. The compared groups did not statistically significantly differ from each other in terms of age, gender, body mass index, clinical picture and duration of symptoms before surgery, assessment of neurological status according to the Zurich Claudication Questionnaire (ZCQ), preoperative diagnosis, localization of stenosis, pain assessment in the back and leg before surgery according to a digital rating scale, physical status (ASA), health assessment (SF-12, ODI), follow-up period, as well as smoking and the presence of comorbidities (p &gt; 0.05). In the OLIF-AF group, compared to the OLIF-PF group, a statistically significant advantage was found in terms of blood loss, duration of surgery and anesthesia, the level of radiological exposure, duration of patient’s hospitalization and hospital stay in the postoperative period, as well as the duration of antibiotic prophylaxis and intraoperative volume of infusions (p &lt; 0.05). Despite earlier discharge and less use of local anesthesia (35.7 % vs 73.3 %; p = 0.001), patients in the OLIF-AF group had statistically significantly lower level of back pain on the day of discharge (3.0 vs 3.5; p = 0.034) and were less likely to need opioids (3.6 % vs 31.7 %; p = 0.003). With regard to complications and adverse events, there were no statistically significant differences during dynamic follow-up period from 3 to 50 months in both groups (17.9 % vs 28.3 %; p = 0.290), including depending on the timing of complications (early or late). In addition, no statistically significant differences were found for neurological, infectious, gastrointestinal, urological, or implant-related complications (p &gt; 0.05).Conclusions. Indirect decompression of the spinal roots and interbody fusion through the lateral pre-psoas approach in combination with OLIF-AF is an effective and safe technique for the surgical treatment of single-segment lumbar stenosis. This method allows to reduce the invasiveness of surgery and severity of the pain syndrome and to create conditions for enhanced recovery after surgery. Further multicenter randomized trials are needed to comprehensively evaluate long-term outcomes.

New horizons in the diagnosis and management of dehydration.

Hydration is a fundamental aspect of clinical practice and yet it is an under-researched topic, particularly in older people, leading to many areas of uncertainty. There are two types of dehydration; hypertonic, which is a water deficit, and isotonic, which is a deficit of both water and salt. Individual clinical signs and bedside tests are poor diagnostic tools, making dehydration difficult to identify. However, the diagnostic value of a holistic clinical approach is not known. The gold-standard clinical test for dehydration is serum osmolality, but this cannot diagnose isotonic dehydration and may delay diagnosis in acute situations. Salivary osmolality point-of-care testing is a promising and rapid new diagnostic test capable of detecting both hypertonic and isotonic dehydration in older people, but further evidence to support its clinical utility is needed. Daily fluid requirements may be less than previously thought in adults, but the evidence specific to older people remains limited. Hydration via the subcutaneous route is safer and easier to initiate than the intravenous route but is limited by infusion speed and volume. Prompting older adults more frequently to drink, offering a wider selection of drinks and using drinking vessels with particular features can result in small increases in oral intake in the short-term. The ongoing clinically-assisted hydration at end of life (CHELsea II) trial will hopefully provide more evidence for the emotive issue of hydration at the end of life.

Revolutionizing IV Infusions: Empowering Care with the DripControl+ App for Real-Time Monitoring and Precision Management

The demand for an effective and precise monitoring and control system for intravenous infusion therapy has increased due to concerns regarding medication errors and inefficiencies associated with current manual monitoring methods employed by nurses, particularly when caring for multiple patients across different rooms. This research aims to enhance intravenous infusion therapy by developing a real-time monitoring and control system. The system utilizes IoT technology and advanced sensors, including the load cell sensor for infusion volume detection, the FC-33 optocoupler sensor for precise infusion drop monitoring, and also a servo motor as an actuator to bend the infusion hose. Integrated with the NodeMCU ESP32 microcontroller, the system empowers healthcare professionals with the user-friendly DripControl+ app to remotely monitor and cont rol the infusion process. The results indicate a seamless collaboration among the system components. The FC-33 Optocoupler sensor exhibits an outstanding accuracy rate of 99.39%. The load cell sensor achieves an impressive 99.61% accuracy. The servo motor precisely follows predetermined positions. These outcomes effectively highlight the system's ability to accurately control the infusion drip rate with exceptional precision. The FC-33 optocoupler sensor and servo motor play crucial roles in achieving this accuracy. With an impressive average accuracy of 97.99%, the system has proven to be highly efficient. However, it should be noted that sudden changes in infusion speed could impact the accuracy of the readings. The future research could focus on refining the system's ability to respond to abrupt changes in infusion speed through advanced algorithms, such as machine learning.