Relative Hypotension Research Articles

Naxitamab-related adverse events within and across treatment cycles in patients with relapsed/refractory (R/R) high-risk neuroblastoma.

10032 Background: Anti-GD2 monoclonal antibodies, including naxitamab, for the treatment of high-risk neuroblastoma (HRNB) are associated with adverse events (AEs), though few studies have characterized their frequency and patterns of presentation. A practical understanding of AEs can help clinicians expect and manage those requiring intervention. In this post hoc analysis, we report the frequency and severity of naxitamab-related AEs across infusions and treatment cycles, based on data from a prespecified interim analysis of Trial 201. Methods: Trial 201 (phase 2, NCT03363373) is investigating naxitamab plus granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with R/R HRNB with residual disease in bone/bone marrow only. Patients with soft tissue or actively progressing disease were excluded. Naxitamab was infused at 3 mg/kg/dose IV on Days (D) 1/3/5 with GM-CSF administered SC on Days -4 to 5 (monthly cycles [C]). Patients (N=74) were evaluated for safety (CTCAE v4.0), with frequency defined as % of patients reporting >1 events. Frequency of AEs of Grade ≥3 were evaluated for C1-C5. Results: Most (81%) naxitamab-related AEs were Grade 1 or 2. Grade ≥3 AEs reported in ≥10% of patients were hypotension (60% of patients), pain (54%), urticaria (19%), bronchospasm (18%), and abdominal pain (16%). The frequency of related hypotension Grade ≥3 (Grade 4, n=3) decreased across cycles, from C1 (47%) to C5 (33%) and across infusions, from C1D1 (43%) to C1D3 (18%) and C1D5 (11%). Similar decreases were seen during C2 to C5. Among patients with Grade ≥3 hypotension, 73% had their first event C1D1, of whom 34% and 31% had their second event C1D3 or C2D1, respectively. The frequency of related pain Grade 3 AEs (all preferred terms with word “pain”) decreased from C1 (53%) to C2 (37%), generally stabilizing thereafter with frequencies consistent across infusions. Most (77%) had their first event C1D1, of whom 82% had a second event C1D3. The frequency of related bronchospasm Grade 3 (no Grade 4 AEs) was relatively stable around 7% from C1 to C3, decreasing to 4% and 2% in C4 and C5, respectively. Patients generally experienced these events on D1 infusions with few reported D3 or D5. No consistent pattern was seen for Grade 3 urticaria. None of the Grade ≥3 AEs of hypotension, urticaria, pain or bronchospasm resulted in treatment discontinuation. Conclusions: The frequency of naxitamab related Grade ≥3 AEs changed over the course of therapy. Hypotension was most frequent C1D1, decreasing across infusions and cycles. Pain frequency peaked C1 and decreased in subsequent cycles, remaining stable across infusions. Bronchospasm events, though relatively rare, generally occurred D1 and decreased across infusions. The results underline the importance of initial and ongoing monitoring within and across cycles to ensure appropriate and timely management. Clinical trial information: NCT03363373 .

Timing of antibiotic treatment identifies distinct clinical presentations among patients presenting with suspected septic shock.

Recent clinical guidelines for sepsis management emphasize immediate antibiotic initiation for suspected septic shock. Though hypotension is a high-risk marker of sepsis severity, prior studies have not considered the precise timing of hypotension in relation to antibiotic initiation and how clinical characteristics and outcomes may differ. Our objective was to evaluate antibiotic initiation in relation to hypotension to characterize differences in sepsis presentation and outcomes in patients with suspected septic shock. Adults presenting to the emergency department (ED) June 2012-December 2018 diagnosed with sepsis (Sepsis-III electronic health record [EHR] criteria) and hypotension (non-resolving for ≥30 min, systolic blood pressure<90mmHg) within 24h. We categorized patients who received antibiotics before hypotension ("early"), 0-60 min after ("immediate"), and>60 min after ("late") treatment. Among 2219 patients, 55% received early treatment, 13% immediate, and 32% late. The late subgroup often presented to the ED with hypotension (median 0 min) but received antibiotics a median of 191 min post-ED presentation. Clinical characteristics notable for this subgroup included higher prevalence of heart failure and liver disease (p<0.05) and later onset of systemic inflammatory response syndrome (SIRS) criteria compared to early/immediate treatment subgroups (median 87 vs. 35 vs. 20 min, p<0.0001). After adjustment, there was no difference in clinical outcomes among treatment subgroups. There was significant heterogeneity in presentation and timing of antibiotic initiation for suspected septic shock. Patients with later treatment commonly had hypotension on presentation, had more hypotension-associated comorbidities, and developed overt markers of infection (eg, SIRS) later. While these factors likely contribute to delays in clinician recognition of suspected septic shock, it may not impact sepsis outcomes.

Safety and Feasibility of Opening Tamsulosin Capsules for Enteral Feeding Tube Administration

Purpose: Tamsulosin is formulated as sustained release beads within a capsule to prevent rapid absorption and associated hypotension. The package insert advises the capsule is swallowed whole; not crushed, chewed, or opened. To our knowledge, there are no current data on opening capsules for adults with enteral tube feeds. Given the unidentified safety and efficacy of administration via enteral tubes, alternative alpha blockers with less selectivity for alpha1A are often used. Methods: A single center retrospective chart review was conducted at two hospital sites. Adult patients that received at least one dose of tamsulosin or doxazosin while an enteral feeding tube was placed were included. Safety outcomes evaluated were the number of documented tube obstructions and incidence of medication associated hypotension. Results: 169 patients were included. Ten enteral feeding tube obstructions were reported, 4 of 110 (3.64%) in the tamsulosin arm and 6 of 59 (10.17%) in the doxazosin arm (RR .36, 95% CI .11 to 1.22, P = .099). At least 1 episode of medication associated hypotension occurred in 22 of 98 (22.45%) in the tamsulosin arm and 20 of 49 (40.82%) in the doxazosin arm (RR .55, 95% CI .33 to .91, P = .019). Conclusion: There was no statistically significant difference in the number of tube obstructions between patients receiving tamsulosin or doxazosin via enteral tube feeds. Patients receiving doxazosin were at increased risk of experiencing medication related hypotension. Tamsulosin capsules may be opened and administered via enteral feeding tubes if administered with content integrity intact.

Interactions between aspirin and ticagrelor during experimental human endotoxaemia

Abstract Introduction Dual antiplatelet therapy (DAPT) with aspirin 75-100mg once daily (OD) and the P2Y12 inhibitor ticagrelor is a standard treatment for acute coronary syndromes. De-escalating DAPT to ticagrelor monotherapy reduces bleeding risk yet appears to have minimal ischaemic penalty in most groups. The reason for this is unclear. P2Y12 inhibition can inhibit inflammatory processes relevant to atherothrombosis but aspirin may hypothetically counter these via platelet PGE2 inhibition. We studied the regimen-dependent effects of aspirin +/- ticagrelor in a human model of endotoxaemia. Endotoxin activates toll-like receptor 4, a key damage receptor in atherogenesis. Methods 72 healthy volunteers were randomised to receive either no aspirin or aspirin 20mg twice daily (BD), 75mg OD or 300mg OD for 10 days +/- a loading dose of ticagrelor on the last day prior to receiving intravenous endotoxin administration (2ng/kg). Blood was collected at 9 timepoints from 1h pre to 6h post endotoxin. Key cytokines and prostanoids in the blood/urine were measured by ELISA, platelet function by light transmittance aggregometry and platelet-leukocyte interaction by flow cytometry. Bleeding time was measured pre and 3h post endotoxin. After &amp;gt;5 weeks, in a 2nd period they received the same dose of aspirin as the 1st but received ticagrelor if they had not already, and vice versa, undergoing a 2nd endotoxin challenge at the end of the period. The primary endpoint was plasma tumour necrosis factor (TNF)-α. Results 72 participants were randomised (median 22.5yrs [range 18-59], 6F:66M). A total of 128 endotoxin challenges were performed. Endotoxaemia was associated with flu-like symptoms, pyrexia, tachycardia and relative hypotension but was safe. In those not receiving aspirin, plasma TNF-α was significantly lower when receiving ticagrelor vs. no ticagrelor, but in those receiving any dose of aspirin the significant effect of ticagrelor was abolished (Fig 1). All doses of aspirin fully suppressed arachidonic acid-induced PA with or without ticagrelor despite the thromboinflammatory stimulus of endotoxaemia (Fig 2A), and significantly augmented the inhibitory effect of ticagrelor on collagen-induced PA (2B). Aspirin 75mg OD and 300mg OD, but not 20mg BD, significantly prolonged bleeding time from baseline (2C). Ticagrelor significantly prolonged bleeding time in combination with any dose of aspirin or no aspirin. Aspirin dose-dependently inhibited PGE2 release. Conclusions All doses of aspirin tested prevented the ability of ticagrelor to significantly inhibit cytokine release during experimental endotoxaemia. Aspirin 20mg BD may offer improved bleeding risk with maintained antiplatelet effect compared to standard regimens. Where ticagrelor monotherapy is an option, dropping aspirin may allow ticagrelor to exert greater beneficial effect on inflammatory pathways relevant to atherothrombosis, potentially reducing ischaemic risk whilst also reducing bleeding risk.Figure 1Figure 2

The effect of relative hypotension on 30-day mortality in older people receiving emergency care

Research has observed increased mortality among older people attending the emergency department (ED) who had systolic pressure > 7 mmHg lower than baseline primary care values. This study aimed to (1) assess feasibility of identifying this ‘relative hypotension’ using readily available ED data, (2) externally validate the 7 mmHg threshold, and (3) refine a threshold for clinically important relative hypotension. A single-centre retrospective cohort study linked year 2019 data for ED attendances by people aged over 64 to hospital discharge vital signs within the previous 18 months. Frailty and comorbidity scores were calculated. Previous discharge (‘baseline’) vital signs were subtracted from initial ED values to give individuals’ relative change. Cox regression analysis compared relative hypotension > 7 mmHg with mean time to mortality censored at 30 days. The relative hypotension threshold was refined using a fully adjusted risk tool formed of logistic regression models. Receiver operating characteristics were compared to NEWS2 models with and without incorporation of relative systolic. 5136 (16%) of 32,548 ED attendances were linkable with recent discharge vital signs. Relative hypotension > 7 mmHg was associated with increased 30-day mortality (HR 1.98; 95% CI 1.66–2.35). The adjusted risk tool (AUC: 0.69; sensitivity: 0.61; specificity: 0.68) estimated each 1 mmHg relative hypotension to increase 30-day mortality by 2% (OR 1.02; 95% CI 1.02–1.02). 30-day mortality prediction was marginally better with NEWS2 (AUC: 0.73; sensitivity: 0.59; specificity: 0.78) and NEWS2 + relative systolic (AUC: 0.74; sensitivity: 0.63; specificity: 0.75). Comparison of ED vital signs with recent discharge observations was feasible for 16% individuals. The association of relative hypotension > 7 mmHg with 30-day mortality was externally validated. Indeed, any relative hypotension appeared to increase risk, but model characteristics were poor. These findings are limited to the context of older people with recent hospital admissions.

Intraoperative Blood Pressure and Carbon Dioxide Values during Aneurysmal Repair and the Outcomes after Aneurysmal Subarachnoid Hemorrhage.

Cerebral autoregulation impairment is a critical aspect of subarachnoid hemorrhage (SAH)-induced secondary brain injury and is also shown to be an independent predictor of delayed cerebral ischemia (DCI) and poor neurologic outcomes. Interestingly, intraoperative hemodynamic and ventilatory parameters were shown to influence patient outcomes after SAH. The aim of the current study was to evaluate the association of intraoperative hypotension and hypocapnia with the occurrence of angiographic vasospasm, DCI, and neurologic outcomes at discharge. Intraoperative data were collected for 390 patients with aneurysmal SAH who underwent general anesthesia for aneurysm clipping or coiling between January 2010 and May 2018. We measured the mean intraoperative blood pressure and end-tidal carbon dioxide (ETCO2), as well as the area under the curve (AUC) for the burden of hypotension: SBP below 100 or MBP below 65 and hypocapnia (ETCO2 < 30), during the intraoperative period. The outcome measures were angiographic vasospasm, DCI, and the neurologic outcomes at discharge as measured by the modified Rankin scale score (an mRS of 0-2 is a good outcome, and 3-6 is a poor outcome). Univariate and logistic regression analyses were performed to evaluate whether blood pressure (BP) and ETCO2 variables were independently associated with outcome measures. Out of 390 patients, 132 (34%) developed moderate-to-severe vasospasm, 114 (29%) developed DCI, and 46% (169) had good neurologic outcomes at discharge. None of the measured intraoperative BP and ETCO2 variables were associated with angiographic vasospasm, DCI, or poor neurologic outcomes. Our study did not identify an independent association between the degree of intraoperative hypotension or hypocapnia in relation to angiographic vasospasm, DCI, or the neurologic outcomes at discharge in SAH patients.

Hypotension during transsphenoidal pituitary surgery associated with increase in plasma levels of brain injury markers.

Patients undergoing pituitary surgery may experience short- and long-term postoperative morbidity. Intraoperative factors such as hypotension might be a contributing factor. Our aim was to investigate the association between intraoperative hypotension and postoperative plasma levels of tau, neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) as markers of perioperative brain injury. Between June 2016 and October 2017, 35 patients from the Gothenburg Pituitary Tumor Study were included. For tau, NfL, and GFAP, concentrations were measured in plasma samples collected before and immediately following surgery, and on postoperative days 1 and 5. The difference between the highest postoperative value and the value before surgery was used for analysis (∆taupeak , ∆NfLpeak , ∆GFAPpeak ). Intraoperative hypotension was defined as the area under the curve of an absolute threshold below 70 mmHg (AUC70) and a relative threshold below 20% (AUC20%) of the baseline mean arterial blood pressure. Plasma tau and GFAP were highest immediately following surgery and on day 1, while NfL was highest on day 5. There was a positive correlation between AUC20% and both ∆taupeak (r2 = .20, p < .001) and ∆NfLpeak (r2 = .26, p < .001). No association was found between AUC20% and GFAP or between AUC70 and ∆taupeak , ∆NfLpeak or ∆GFAPpeak . Intraoperative relative, but not absolute, hypotension was associated with increased postoperative plasma tau and NfL concentrations. Patients undergoing pituitary surgery may be vulnerable to relative hypotension, but this needs to be validated in future prospective studies.

A preoperative ultrasound-based protocol for optimisation of fluid therapy to prevent early intraoperative hypotension: a randomised controlled study

BackgroundIntraoperative hypotension is a risk factor for postoperative complications. Preoperative dehydration is a major contributor, although it is difficult to estimate its severity. Point-of-care ultrasound offers several potential methods, including measurements of the inferior vena cava. The addition of lung ultrasound may offer a safety limit. We aimed to evaluate whether the implication of an ultrasound-based preoperative fluid therapy protocol can decrease the incidence of early intraoperative hypotension.MethodsRandomised controlled study in a tertiary university department involves elective surgical patients of ASA 2–3 class, scheduled for elective major abdominal surgery under general anaesthesia with intubation. We randomised 40–40 patients; 38–38 were available for analysis. Conventional fluid therapy was ordered on routine preoperative visits. Ultrasound-based protocol evaluated the collapsibility index of inferior vena cava and lung ultrasound profiles. Scans were performed twice: 2 h and 30 min before surgery. A high collapsibility index (≥ 40%) indicated a standardised fluid bolus, while the anterior B-profile of the lung ultrasound contraindicated further fluid. The primary outcome was the incidence of postinduction and early intraoperative (0–10 min) hypotension (MAP < 65 mmHg and/or ≥ 30% of decrease from baseline). Secondary endpoints were postoperative lactate level, urine output and lung ultrasound score at 24 h.ResultsThe absolute criterion of postinduction hypotension was fulfilled in 12 patients in the conventional group (31.6%) and 3 in the ultrasound-based group (7.9%) (p = 0.0246). Based on composite criteria of absolute and/or relative hypotension, we observed 17 (44.7%) and 7 (18.4%) cases, respectively (p = 0.0136). The incidence of early intraoperative hypotension was also lower: HR for absolute hypotension was 2.10 (95% CI 1.00–4.42) in the conventional group (p = 0.0387). Secondary outcome measures were similar in the study groups.ConclusionWe implemented a safe and effective point-of-care ultrasound-based preoperative fluid replacement protocol into perioperative care.Trial registrationThe study was registered to ClinicalTrials.gov on 10/12/2021, registration number: NCT05171608 (registered prospectively on 10/12/2021).

A case of abdominal distress and kidney dysfunction in a patient with diabetes.

A 65-year-old male with diabetes mellitus and dyslipidemia presented with a fever and dysuria for the past week. He developed hematuria, lower abdominal discomfort, and constipation. During examination, tachycardia (120 beats per min) and relative hypotension (96/57 mmHg) were observed. Laboratory tests revealed acute kidney injury with metabolic acidosis (serum creatinine of 5.47 mg/dL, pH value 7.29 BE: −7.7). Kidney, ureter, and bladder imaging showed bladder distension with gas formation (Figure 1). An abdominal computed tomography scan revealed emphysematous cystitis (Figure 2). The patient was initially treated with foley irrigation and antibiotics, but he developed respiratory distress on the same day and was intubated for urosepsis. Blood and urine cultures showed Klebsiella pneumoniae. He received temporary hemodialysis due to refractory fluid overload and Kidney Disease Improving Global Outcomes (KDIGO) stage III acute kidney injury by serum creatinine criteria during hospitalization. Emphysematous urinary tract infections (UTIs) involve gas formation in the urinary tract and are commonly caused by Escherichia coli or Klebsiella pneumoniae, particularly in individuals with diabetes.1 Emphysematous cystitis is a rare type of UTI characterized by gas formation in the bladder wall. The symptoms include abdominal pain, dysuria, and pneumaturia. The diagnosis is made through imaging, and treatment involves antibiotics.2 In severe cases, hospitalization may be required. Emphysematous cystitis is a rare but serious complication of UTIs, particularly in individuals with diabetes. Early diagnosis and appropriate management, including antibiotics and surgical therapy, if necessary, are essential for improving outcomes.3 Patients or the public were not involved in the design, conduct, reporting, or dissemination plans of our research.

Ultrasound-guided anterior iliopsoas muscle space block effectively reduces intraoperative hypotension in elderly adults undergoing hip surgery: A randomised controlled trial.

Hypotension often occurs during hip surgery in elderly adults with conventional posterior lumbosacral plexus block. We conducted a randomised controlled trial to determine if simple iliopsoas space block can lower the incidence of intraoperative hypotension (IOH) and provide sufficient perioperative pain relief during hip fracture surgery in elderly adults. Patients undergoing surgery for elderly hip fracture were randomised to receive either an anterior iliopsoas space block with a lateral femoral cutaneous nerve block or a posterior lumbosacral plexus block. The primary outcome was a composite measure of IOH incidence comprising frequency, absolute and relative hypotension durations. Compared to the posterior group, the iliopsoas space block group had a decreased median frequency of IOH [1.09 (0-2. 14) vs. 3 (1.6-4.8), p = 0.001, respectively] along with lower absolute [5 (0-10) min] and relative [minutes below systolic blood pressure of 100 mmHg in % of total anaesthesia time, 6.67 (0-7.65)] duration of IOH compared to the posterior group [35 (10-45) min, p = 0.008; 37.6 (12.99-66.18), p = 0.004, respectively]. The median pain levels in the post-anaesthesia care unit and median intraoperative sufentanil usage were comparable between the iliopsoas space group [2 (1-3); 8 (6-10) μg] and posterior group [1 (0-3); 5 (5-8) μg]. Thermal imaging revealed that the limb injected with the iliopsoas space block had a higher skin temperature than the unblocked limb in the sacral plexus innervated region. A single iliopsoas space block lowers the IOH incidence and provides comparable perioperative analgesia to conventional lumbosacral plexus block. Trial registration at www.chictr.org.cn (ChiCTR2100051394); registered 22 September 2021.

A RARE CASE OF PROTRACTED ANAPHYLAXIS CAUSED BY ACETAMINOPHEN

<h3>Introduction</h3> Acetaminophen is a rare but recognized etiology of anaphylaxis. We present an unusual case of protracted anaphylaxis requiring intensive care unit (ICU) monitoring following intravenous (IV) acetaminophen. <h3>Case Description</h3> A 49-year-old female with a history of ovarian cancer presented to the emergency department with pruritic urticarial rash, fevers, tachycardia, and relative hypotension. A sepsis workup was initiated. Hemodynamics improved with broad-spectrum antibiotics and fluids. Due to symptomatic high-grade fevers, IV acetaminophen was administered. Her rash, tachycardia, and relative hypotension worsened one hour following infusion. Despite resuscitation with diphenhydramine and fluids, she remained tachycardic and febrile, prompting treatment for suspected anaphylaxis with intramuscular epinephrine, corticosteroids, and additional diphenhydramine. Her rash and hemodynamics improved moderately. She was subsequently started on norepinephrine and transferred to the medical ICU, where she had two days of persistent tachycardia and fluctuating urticarial rash responsive to antihistamines. Infectious workup was unrevealing. She later revealed a prior history of urticaria following home oral acetaminophen. Tryptase drawn one hour after decompensation was elevated to 23.8 mcg/L (baseline 3.2 mcg/L). The diagnosis was made of IgE-mediated reaction to acetaminophen causing protracted anaphylaxis. <h3>Discussion</h3> Anaphylaxis secondary to acetaminophen is an uncommon but recognized phenomenon. An initial differential included pseudoallergic reaction, given acetaminophen can be a weak cyclooxygenase-1 inhibitor causing direct mast cell activation and urticaria; however, this does not classically cause hypotension. Overall, this presentation may represent a mixed picture of sepsis of unclear etiology with superimposed IgE-mediated reaction. It is important to recognize anaphylaxis can co-exist with sepsis and manifest with overlapping symptoms.

A Single Dosage of l-Arginine Oral Supplementation Induced Post-Aerobic Exercise Hypotension in Hypertensive Patients

Lowering of peripheral vascular resistance is one of the primary processes involved in blood pressure decrease. Nitric oxide plays a significant role in this process and the availability of l-arginine is a crucial element in nitric oxide biosynthesis. Oral l-arginine supplementation may therefore be a potentiating element in post-exercise hypotension, mediated by its vasodilator action. Thus, the purpose of this study was to investigate if a single dose of l-arginine oral supplementation might impact the post-aerobic exercise blood pressure responses in treated hypertensive individuals. A double-blind, randomized, placebo-controlled crossover trial was conducted. The sample included male (4) and female (6) subjects [62 ± 10 years]. The participants were randomized to ingest one sachet containing 8 grams of l-arginine or placebo (corn starch) dissolved in water (100 ml). The substances were self-administered 120 min before the experimental or control session. The exercise was conducted on a treadmill and consisted of: a 5 min warm-up (50-65% HRreserve); 40 min of running/walking at 60-70% HRreserve; and a 5 min progressive cooldown. After the exercise sessions, blood pressure was measured every 10 min for 60 min. The l-arginine supplementation arm led to significant post-exercise systolic hypotension (mean post-exercise) in relation to rest period (117 ± 12 vs 125 ± 15 mmHg - p = 0.004 [l-arginine] and 121 ± 11 vs 125 ± 15 - p = 0.341 [placebo]). In addition, a systolic net effect of −6.9 ± 3.6 mmHg [p = 0.046] was identified for the mean post-exercise values. Therefore, this study showed that a single dosage of l-arginine oral supplementation induced post-aerobic exercise hypotension in hypertensive patients.

Cardiovascular and hemodynamic consequences of recombinant placental growth factor administration in Guinea pigs

ABSTRACT Placental growth factor (PlGF), a member of the vascular endothelial growth factor family of proteins regulating angiogenesis, has been shown to have acute vasodilatory effects on human resistance arteries. However, the acute hemodynamic effects of PlGF in vivo are not known. The aim of this study was to report acute cardiovascular changes induced by recombinant human PlGF administered intravenously in male Guinea Pigs with implanted telemeters. PlGF decreased mean arterial blood pressure by 10–20% within minutes. The magnitude of reduction was similar at three dose levels; however, the duration of relative hypotension was dose-dependent. Blood pressure reduction resulted in a compensatory increase in heart rate, or reflex tachycardia. To rule out any direct effect on the heart, PlGF was tested in the ex vivo Langendorff heart preparation, and no cardiac changes were found. Together these results suggest that the PlGF-related changes in blood pressure are largely mediated by its actions in the vasculature.

Effects of the timing and intensity of treatment on septic shock patients treated with CytoSorb®: Clinical experience.

A group of adult septic shock patients treated with hemoperfusion (HA) with the Cytosorb® associated with CVVHD were studied to determine (a) the effects of this technique on different clinical variables; and (b) the impact of the pre CytoSorb® interval and its intensity on the outcome. The catecholamine index (CI) and the pressure-catecholamine Index (PCAI) were used to assess the amount of catecholamine administered at baseline and during the procedure, respectively. The pre-treatment time was calculated since the onset of the septic-shock related hypotension and the initiation of the first session and the intensity was assessed considering either the total volume of blood processed and the duration of the HA. Overall, 51 patients with septic shock (30 m, 21 f), age 68 years (IQR 59-76) were retrospectively enrolled in the study; 26 were discharged alive form the ICU (S) and 25 died in ICU (NS); in the S group either CI and PCAI decreased significantly but in NS the CI increased and the PCAI remained stable in NS. In S, the time elapsing from the onset of symptoms and the start of Cytosorb® was shorter than in NS; the duration of the treatment and the volume of blood processed were significantly higher in S than in NS. In this group of septic shock patients, the earlier initiation of Cytosorb®, its longer duration and the higher volume of blood processed were associated with a better survival.

This Month in Anesthesiology

This Month in Anesthesiology

Clinical and Laboratory Diagnostic Features of Kyasanur Forest Disease: A Study From Wayanad, South India

BackgroundKyasanur forest disease (KFD), also known as monkey fever, was first recognized in the Shimoga district of Karnataka, India, in 1957. This study was conceived to address the paucity of medical literature on KFD, to describe the clinical and laboratory features of real-time reverse-transcriptase-polymerase chain reaction (rRT-PCR) confirmed cases of KFD, and to detect any change in the clinical picture and presentation of the disease over the last 30 years.AimThe study sought to document the clinical and laboratory features of Kyasanur forest disease (KFD), a tick-borne arboviral disease, now emerging in many parts of southern India.Material and methodsThis was a retrospective study using secondary data of patients with real-time reverse transcription-polymerase chain reaction (rRT-PCR)-confirmed KFD in a secondary care hospital in Wayanad, Kerala, India.ResultsSixty rRT-PCR-proven KFD patients were included in the study. Commonly noted clinical symptoms were fever (98%), headache (80%), body ache (86%), vomiting (61%), and prostration (83%). Relative bradycardia, hypotension (45%), and oral lesions (23%) were the frequent physical signs. The median total leukocyte count and median platelet count at admission were 2600 per μL and 1.62 per μL, respectively. The median erythrocyte sedimentation rate was 10 mm/hr. Urinary sediments and albuminuria were seen in 66% and 60% respectively. The major complications observed were neurological complications (23%), bleeding manifestations (20%), and persistent shock (20%). The common neurological complications were seizures, altered sensorium, aseptic meningitis, and focal neurological deficits. The case fatality rate in the study was 6.7%.ConclusionsThe clinical picture of a prostrating viral syndrome in an epidemiological setting of KFD with marked leucopenia, moderate thrombocytopenia, low erythrocyte sedimentation rate (ESR), albuminuria, urinary sediments, and moderately elevated transaminases help in making an early diagnosis of KFD. Neurological complications in the initial two weeks are associated with poor outcomes.

The impact of relative hypotension on acute kidney injury progression after cardiac surgery: a multicenter retrospective cohort study

BackgroundCardiac surgery is performed worldwide, and acute kidney injury (AKI) following cardiac surgery is a risk factor for mortality. However, the optimal blood pressure target to prevent AKI after cardiac surgery remains unclear. We aimed to investigate whether relative hypotension and other hemodynamic parameters after cardiac surgery are associated with subsequent AKI progression.MethodsWe retrospectively enrolled adult patients admitted to 14 intensive care units after elective cardiac surgery between January and December 2018. We defined mean perfusion pressure (MPP) as the difference between mean arterial pressure (MAP) and central venous pressure (CVP). The main exposure variables were time-weighted-average MPP-deficit (i.e., the percentage difference between preoperative and postoperative MPP) and time spent with MPP-deficit > 20% within the first 24 h. We defined other pressure-related hemodynamic parameters during the initial 24 h as exploratory exposure variables. The primary outcome was AKI progression, defined as one or more AKI stages using Kidney Disease: Improving Global Outcomes’ creatinine and urine output criteria between 24 and 72 h. We used multivariable logistic regression analyses to assess the association between the exposure variables and AKI progression.ResultsAmong the 746 patients enrolled, the median time-weighted-average MPP-deficit was 20% [interquartile range (IQR): 10–27%], and the median duration with MPP-deficit > 20% was 12 h (IQR: 3–20 h). One-hundred-and-twenty patients (16.1%) experienced AKI progression. In the multivariable analyses, time-weighted-average MPP-deficit or time spent with MPP-deficit > 20% was not associated with AKI progression [odds ratio (OR): 1.01, 95% confidence interval (95% CI): 0.99–1.03]. Likewise, time spent with MPP-deficit > 20% was not associated with AKI progression (OR: 1.01, 95% CI 0.99–1.04). Among exploratory exposure variables, time-weighted-average CVP, time-weighted-average MPP, and time spent with MPP < 60 mmHg were associated with AKI progression (OR: 1.12, 95% CI 1.05–1.20; OR: 0.97, 95% CI 0.94–0.99; OR: 1.03, 95% CI 1.00–1.06, respectively).ConclusionsAlthough higher CVP and lower MPP were associated with AKI progression, relative hypotension was not associated with AKI progression in patients after cardiac surgery. However, these findings were based on exploratory investigation, and further studies for validating them are required.Trial Registration UMIN-CTR, https://www.umin.ac.jp/ctr/index-j.htm, UMIN000037074.

Comparison between continuous rate infusion and target-controlled infusion of propofol in dogs: a randomized clinical trial

ObjectiveTo compare a propofol continuous rate infusion (CRI) with a target-controlled infusion (TCI) in dogs. Study designRandomized prospective double-blinded clinical study. AnimalsA total of 38 healthy client-owned dogs. MethodsDogs premedicated intramuscularly with acepromazine (0.03 mg kg–1) and an opioid (pethidine 3 mg kg–1, morphine 0.2 mg kg–1 or methadone 0.2 mg kg–1) were allocated to P-CRI group (propofol 4 mg kg–1 intravenously followed by CRI at 0.2 mg kg–1 minute–1), or P-TCI group [propofol predicted plasma concentration (Cp) of 3.5 μg mL–1 for induction and maintenance of anaesthesia via TCI]. Plane of anaesthesia, heart rate, respiratory rate, invasive blood pressure, oxygen haemoglobin saturation, end-tidal carbon dioxide and body temperature were monitored by an anaesthetist blinded to the group. Numerical data were analysed by unpaired t test or Mann–Whitney U test, one-way analysis of variance and Dunnett’s post hoc test. Categorical data were analysed with Fisher’s exact test. Significance was set for p < 0.005. ResultsOverall, propofol induced a significant incidence of relative hypotension (mean arterial pressure 20% below baseline, 45%), apnoea (71%) and haemoglobin desaturation (65%) at induction of anaesthesia, with a higher incidence of hypotension and apnoea in the P-CRI than P-TCI group (68% versus 21%, p = 0.008; 84% versus 58%, p = 0.0151, respectively). Propofol Cp was significantly higher at intubation in the P-CRI than P-TCI group (4.83 versus 3.5 μg mL–1, p < 0.0001), but decreased during infusion, while Cp remained steady in the P-TCI group. Total propofol administered was similar between groups. Conclusions and clinical relevanceBoth techniques provided a smooth induction of anaesthesia but caused a high incidence of side effects. Titration of anaesthesia with TCI caused fewer fluctuations in Cp and lower risk of hypotension compared with CRI.

Impact of SGLT2 inhibitors on major clinical events and safety outcomes in heart failure patients: a meta-analysis of randomized clinical trials.

BACKGROUNDSodium-glucose co-transporter-2 inhibitors (SGLT2i) significantly reduce the risk of cardiovascular (CV) and renal adverse events in patients with diabetes mellitus, heart failure (HF) and/or chronic kidney disease. We performed a meta-analysis to explore the impact of several different SGLT2i on all-cause mortality, CV mortality, HF hospitalizations and the combined outcome CV death/HF hospitalization in HF patients across the spectrum of left ventricular ejection fraction (LVEF) phenotypes.METHODSA systematic search in MEDLINE database and Cochrane library through March 2021 was performed without limitations. Randomized clinical trials that provided data about the impact of SGLT2i on all-cause mortality, CV mortality, HF hospitalizations or the combined outcome of CV death/HF hospitalization in HF patients were included. A random effects model was used for calculating the effect estimates.RESULTSNine studies (n = 16,723 patients, mean age: 65.9 years, males: 70.7%) were included in the quantitative synthesis. Compared to placebo, SGLT2i use was associated with 14% lower risk of all-cause mortality [hazard ratio (HR) = 0.86, 95% CI: 0.78−0.94,I2 = 0, P = 0.0008], 32% lower risk of HF hospitalizations (HR = 0.68, 95% CI: 0.62−0.74,I2 = 0, P < 0.001), 14% lower risk of CV mortality (HR = 0.86, 95% CI: 0.77−0.95, I2 = 0, P = 0.003) and 26% lower risk of CV death/HF hospitalization (HR = 0.74, 95% CI: 0.68−0.80,I2 = 0, P < 0.001). Regarding the safety outcomes, our data revealed no significant differences between SGLT2i and placebo groups in drug related discontinuations, amputations, severe hypoglycemia, hypotension, volume depletion, ketoacidosis and genital infections. By contrast, a protective role of SGLT2i against placebo was found for serious adverse events and acute kidney injury. CONCLUSIONSIn patients with HF, regardless of LVEF phenotype, all SGLT2i had an excellent safety profile and significantly reduced the risk of all-cause mortality, CV mortality, HF hospitalizations and CV deaths/HF hospitalizations compared to placebo.

S2261 An Unexpected Cause of Gastrointestinal Bleeding: A Birthday Surprise

Introduction: Infrequently, basic procedures can turn into complex cases due to unforeseen circumstances. It is important for providers to recognize when standard techniques may be inadequate and more creative techniques should be implemented. Case Description/Methods: A 67-year-old male with a past medical history of poliomyelitis, developmental delay, mechanical aortic valve replacement on warfarin, and seizure disorder was transported from his group living facility to the emergency room due to melena. The patient was nonverbal at baseline, so his history was obtained via telephone from his case manager who reported he had developed weakness and fecal incontinence the morning prior to his admission. Stools were reportedly “bloody and black” in color. There was no reported epistaxis. He had been admitted to a nearby hospital two weeks prior for melena with an INR of 21. EGD reportedly showed duodenitis and colonoscopy was not performed. His discharge Hb was 11.5 g/dL. On examination, the patient was resting in the hospital bed comfortably, indicating that he was hungry. Vital signs were notable for relative hypotension compared to his baseline pressure. There was a large scab in his left nare, no oropharyngeal lesions, and his abdomen was soft and nontender to palpation. Rectal exam revealed nonbleeding external hemorrhoids and melena in the rectal vault. Hemoglobin was 9.4 g/dL, BUN 47, and INR 3.1. EGD was notable for a 4cm hard plastic “cupcake topper” in the stomach, no active bleeding, and multiple clots. Attempts to remove the object were unsuccessful due to its large diameter and unmalleable quality which prevented removal via the esophagus or overtube. The foreign body was successfully removed a few days later via fragmentation with a biliary lithotripsy device. Discussion: This case highlights how standard procedures such as GI bleed management can be impacted by unforeseen circumstances, the importance of recognizing when standard endoscopic techniques may not be feasible, and how endoscopic instruments can be utilized for alternative purposes. Although the patient was able to somehow swallow the foreign body, the object was unable to be safely removed en bloc without causing significant esophageal tearing. Because the object’s diameter was >2.5cm, there was low likelihood it would pass into the duodenum, allowing time to plan the optimal extraction technique.Figure 1.: A: Gross photo of macroglossic tongue. B: MRI with contrast of demonstrating macroglossia in the sagittal view.