Various vaccines were developed to reduce the spread of the Severe Acute Respiratory Syndrome Cov-2 (SARS-CoV-2) virus. Quickly after the start of vaccination, reports emerged that anti-SARS-CoV-2 ...vaccines, including ChAdOx1-S, could be associated with an increased risk of thrombosis. We investigated the hemostatic changes after ChAdOx1-S vaccination in 631 health care workers. Blood samples were collected 32 days on average after the second ChAdOx1-S vaccination, to evaluate hemostatic markers such as D-dimer, fibrinogen, α2-macroglobulin, FVIII and thrombin generation. Endothelial function was assessed by measuring Von Willebrand Factor (VWF) and active VWF. IL-6 and IL-10 were measured to study the activation of the immune system. Additionally, SARS-CoV-2 anti-nucleoside and anti-spike protein antibody titers were determined. Prothrombin and fibrinogen levels were significantly reduced after vaccination (−7.5% and −16.9%,
p
< 0.0001). Significantly more vaccinated subjects were outside the normal range compared to controls for prothrombin (42.1% vs. 26.4%,
p
= 0.026) and antithrombin (23.9% vs. 3.6%,
p
= 0.0010). Thrombin generation indicated a more procoagulant profile, characterized by a significantly shortened lag time (−11.3%,
p
< 0.0001) and time-to-peak (−13.0% and
p
< 0.0001) and an increased peak height (32.6%,
p
= 0.0015) in vaccinated subjects compared to unvaccinated controls. Increased VWF (+39.5%,
p
< 0.0001) and active VWF levels (+24.1 %,
p
< 0.0001) pointed toward endothelial activation, and IL-10 levels were significantly increased (9.29 pg/mL vs. 2.43 pg/mL,
p
= 0.032). The persistent increase of IL-10 indicates that the immune system remains active after ChAdOx1-S vaccination. This could trigger a pathophysiological mechanism causing an increased thrombin generation profile and vascular endothelial activation, which could subsequently result in and increased risk of thrombotic events.
Near-infrared spectroscopy non-invasively measures regional cerebral oxygen saturation. Intraoperative cerebral desaturations have been associated with worse neurological outcomes. We investigated ...whether perioperative cerebral desaturations are associated with postoperative delirium in older patients after cardiac surgery.
Patients aged 70 yr and older scheduled for on-pump cardiac surgery were included between 2015 and 2017 in a single-centre, prospective, observational study. Baseline cerebral oxygen saturation was measured 1 day before surgery. Throughout surgery and after ICU admission, cerebral oxygen saturation was monitored continuously up to 72 h after operation. The presence of delirium was assessed using the confusion assessment method for the ICU. Association with delirium was evaluated with unadjusted analyses and multivariable logistic regression.
Ninety-six of 103 patients were included, and 29 (30%) became delirious. Intraoperative cerebral oxygen saturation was not significantly associated with postoperative delirium. The lowest postoperative cerebral oxygen saturation was lower in patients who became delirious (P=0.001). The absolute and relative postoperative cerebral oxygen saturation decreases were more marked in patients with delirium (13 6% and 19 9%, respectively) compared with patients without delirium (9 4% and 14 5%; P=0.002 and P=0.001, respectively). These differences in cerebral oxygen saturation were no longer present after excluding cerebral oxygen saturation values after patients became delirious. Older age, previous stroke, higher EuroSCORE II, lower preoperative Mini-Mental Status Examination, and more substantial absolute postoperative cerebral oxygen saturation decreases were independently associated with postoperative delirium incidence.
Postoperative delirium in older patients undergoing cardiac surgery is associated with absolute decreases in postoperative cerebral oxygen saturation. These differences appear most detectable after the onset of delirium.
NCT02532530.
Abstract Even in present day pain therapy, neuropathic pain remains a challenge for clinicians to treat and a challenge for researchers to investigate. Different animal models have been developed to ...mimic neuropathic pain. Neurotrophins such as nerve growth factor, brain-derived neurotrophic factor and neurotrophin 3 have been studied extensively in these models, yet few review articles concerning brain-derived neurotrophic factor have been published. This article reassesses the literature concerning brain-derived neurotrophic factor expression in the sciatic nerve chronic constriction injury model, the sciatic nerve transection model, the spinal nerve ligation model and the spinal nerve transection model and discusses differences in regulation of brain-derived neurotrophic factor between these models and their causality with neuropathic pain.
MP4OX (oxygenated polyethylene glycol-modified hemoglobin) is a novel oxygen therapeutic agent specifically developed to perfuse and oxygenate tissue at risk for ischemia and hypoxia. In this study, ...we investigated the ability of MP4OX to treat hypotensive episodes. In addition, the tolerability profile of MP4OX in a large surgical population was established.
Patients from 21 study sites in 5 countries, scheduled to undergo primary hip arthroplasty under spinal anesthesia, were randomized in a double-blind manner to receive MP4OX or hydroxyethyl starch (HES) solution (Voluven®; HES 130/0.4). Patients received the first 250-mL dose of investigational product when systolic blood pressure decreased to the predefined dosing trigger. A second 250-mL dose was given only if the systolic blood pressure decreased to the same trigger level after administration of the first dose. The primary efficacy outcome was total duration of all hypotensive episodes during surgery and the first 6 hours after skin closure.
Of the 474 patients randomized, 405 reached the dosing trigger and received at least 1 dose. The mean total duration of all hypotensive episodes was significantly shorter (P < 0.0001) in the MP4OX group (52.4 ± 71.50 minutes; range, 3-442 minutes) compared with the HES group (137.6 ± 120.21 minutes; range, 5-435 minutes). The overall incidence of adverse events (AEs) in the intent-to-treat population was similar between the MP4OX and HES groups (75.2% vs 73.4%; P = 0.733). Transient increases in laboratory values were reported in more patients in the MP4OX group versus HES controls for aspartate aminotransferase (13.4% vs 7.4%; P = 0.052), alanine aminotransferase (6.9% vs 4.9%; P = 0.409), lipase (9.7% vs 3.6%; P = 0.015), and troponin (8.1% vs 2.0%; P = 0.006). There was no significant difference in the incidence of serious AEs reported (6.4% in MP4OX group vs 3.0% in HES controls; P = 0.106). Certain AEs did occur more frequently in the MP4OX group, including nausea (23.8% vs 14.3%; P = 0.016), bradycardia (14.9% vs 5.9%; P = 0.003), hypertension (8.4% vs 2.5%; P = 0.009), and oliguria (5.9% vs 1.5%; P = 0.019). The composite morbidity and ischemia end points did not reveal any differences between the 2 treatment groups.
Administration of MP4OX achieved the end point of treating perioperative hypotension in patients undergoing primary hip arthroplasty under spinal anesthesia. The study was not powered to demonstrate clinical benefit based on the composite morbidity or ischemia outcomes. Although efficacy end points with sufficient power were met, MP4OX is not being proposed for use in routine surgery where the risk-benefit profile would not be favorable based on the safety profile demonstrated in this study.
BACKGROUND:Less than 50% of patients experience sufficient pain relief with current drug therapy for neuropathic pain. Minocycline shows promising results in rodent models of neuropathic pain but was ...not studied in humans with regard to the treatment of neuropathic pain.
METHODS:In this randomized, double-blind, placebo-controlled clinical trial, patients with subacute lumbar radicular pain received placebo, amitriptyline 25 mg, or minocycline 100 mg once a day (n = 20 per group) for 14 days. Primary outcome measure was the pain intensity in the leg as measured by a numeric rating scale ranging from 0 to 10 on days 7 and 14. Secondary outcome measures were the reduction of neuropathic pain symptoms in the leg as determined with a neuropathic pain questionnaire, consumption of rescue medication, and adverse events on days 7 and 14.
RESULTS:Sixty patients were randomized and included in an intention-to-treat analysis. After 14 days, patients in the minocycline and amitriptyline groups reported a reduction of 1.47 (95% confidence interval, 0.16–2.83; P = 0.035) and 1.41 (95% confidence interval, 0.05–2.78; P = 0.043), respectively, in the numeric rating scale compared to the placebo group. No differences were seen in the neuropathic pain questionnaire values at any time point during treatment between the three groups. The rate of adverse events in the amitriptyline group was 10% versus none in the minocycline and placebo groups. No differences were noted in the consumption of rescue medication.
CONCLUSIONS:Although both groups differed from placebo, their effect size was small and therefore not likely to be clinically meaningful.
By maintaining sufficient cerebral blood flow and oxygenation, the goal of cardiopulmonary resuscitation (CPR) is to preserve the pre-arrest neurological state. To date, cerebral monitoring abilities ...during CPR have been limited. Therefore, we investigated the time-course of cerebral oxygen saturation values (rSO₂) during advanced life support in out-of-hospital cardiac arrest. Our primary aim was to compare rSO₂ values during advanced life support from patients with return of spontaneous circulation (ROSC) to patients who did not achieve ROSC.
We performed an observational study to measure rSO₂ using Equanox (Nonin, Plymouth, MI) from the start of advanced life support in the pre-hospital setting.
rSO₂ of 49 consecutive out-of-hospital cardiac arrest patients were analyzed. The total increase from initial rSO₂ value until two minutes before ROSC or end of advanced life support efforts was significantly larger in the group with ROSC 16% (9 to 36) compared to the patients without ROSC 10% (4 to 15) (P = 0.02). Mean rSO₂ from the start of measurement until two minutes before ROSC or until termination of advanced life support was higher in patients with ROSC than in those without, namely 39% ± 7 and 31% ± 4 (P = 0.05) respectively.
During pre-hospital advanced life support, higher increases in rSO₂ are observed in patients attaining ROSC, even before ROSC was clinically determined. Our findings suggest that rSO₂ could be used in the future to guide patient tailored treatment during cardiac arrest and could therefore be a surrogate marker of the systemic oxygenation state of the patient.
Abstract Aim of the study This observational study was performed to assess the cerebral tissue oxygen saturation during and after therapeutic hypothermia in comatose patients after out-of-hospital ...cardiac arrest. Methods We performed a prospective observational study on the cerebral tissue oxygen saturation (SctO2 ) in post-cardiac arrest patients treated with therapeutic hypothermia (TH) between March 2011 and April 2012. SctO2 (measured by near-infrared spectroscopy) was non-invasively and continuously measured in 28 post-cardiac arrest patients during hypothermia and active rewarming. Results At the start of mechanically induced TH, SctO2 was 68% (65–72) and PaCO2 was 47.2 mmHg (36.9 – 51.4). SctO2 and PaCO2 significantly decreased to 59% (57–64; p = 0.006) and 36.6 mmHg (33.9–44.7; p = 0.002), respectively, within the first 3 h of mechanically induced TH. Cerebral tissue oxygen saturation was significantly lower in non-survivors ( n = 10) compared with survivors ( n = 18) at 3 h after induction of hypothermia ( p = 0.02) while the decrease in PaCO2 was similar in both groups. During TH maintenance, SctO2 gradually returned to baseline values (69% (63–72)) at 24 h, with no differences between survivors and non-survivors ( p = 0.65). Carbon dioxide remained within the range of mild hypocapnia (32–38 mmHg) throughout the hypothermic period. During rewarming, SctO2 further increased to 71% (67–78). Conclusions Induction of TH in comatose post-CA patients changes the balance between oxygen delivery and supply. The decrease in SctO2 was less pronounced in patients surviving to hospital discharge.
Current monitoring during cardiopulmonary resuscitation (CPR) is limited to clinical observation of consciousness, breathing pattern and presence of a pulse. At the same time, the adequacy of ...cerebral oxygenation during CPR is critical for neurological outcome and thus survival. Cerebral oximetry, based on near-infrared spectroscopy (NIRS), provides a measure of brain oxygen saturation. Therefore, we examined the feasibility of using NIRS during CPR.
Recent technologies (FORE-SIGHT™ and EQUANOX™) enable the monitoring of absolute cerebral tissue oxygen saturation (SctO2) values without the need for pre-calibration. We tested both FORE-SIGHT™ (five patients) and EQUANOX Advance™ (nine patients) technologies in the in-hospital as well as the out-of-hospital CPR setting. In this observational study, values were not utilized in any treatment protocol or therapeutic decision. An independent t-test was used for statistical analysis.
Our data demonstrate the feasibility of both technologies to measure cerebral oxygen saturation during CPR. With the continuous, pulseless near-infrared wave analysis of both FORE-SIGHT™ and EQUANOX™ technology, we obtained SctO2 values in the absence of spontaneous circulation. Both technologies were able to assess the efficacy of CPR efforts: improved resuscitation efforts (improved quality of chest compressions with switch of caregivers) resulted in higher SctO2 values. Until now, the ability of CPR to provide adequate tissue oxygenation was difficult to quantify or to assess clinically due to a lack of specific technology. With both technologies, any change in hemodynamics (for example, ventricular fibrillation) results in a reciprocal change in SctO2. In some patients, a sudden drop in SctO2 was the first warning sign of reoccurring ventricular fibrillation.
Both the FORE-SIGHT™ and EQUANOX™ technology allow non-invasive monitoring of the cerebral oxygen saturation during CPR. Moreover, changes in SctO2 values might be used to monitor the efficacy of CPR efforts.
Background
The objective of this study was to describe changes in cerebral tissue oxygen saturation (SctO
2
) due to changes in body position in healthy volunteers and in patients undergoing surgery ...under general anesthesia in the beach chair position (BCP) and lateral decubitus position (LDP).
Methods
In this prospective observational study, SctO
2
was measured in 85 awake volunteers serially positioned every 15 min, beginning with the supine position (SP) and followed by the beach chair, supine, and lateral decubitus positions. Cerebral tissue oxygen saturation was also measured supine and in either the BCP or the LDP in 195 patients (according to surgical preference) undergoing elective arthroscopic shoulder surgery. We measured the lowest stable SctO
2
values in each position as well as changes in blood pressure and heart rate.
Results
In healthy volunteers, the median (interquartile range IQR) lowest stable SctO
2
value in the SP was 69 66-71 %. A change in position to the BCP caused a small but statistically significant decrease in the median IQR lowest SctO
2
value to 67 65-70 % (
P
= 0.028 compared with baseline). This decrease was associated with an increase in median IQR arterial pressure from 83 78-88 mmHg in the SP to 85 81-93 mmHg in the BCP (
P
< 0.001 compared with baseline). In patients undergoing surgery in the BCP, the median IQR lowest stable SctO
2
value was 55 51-59 %, which was significantly lower (
P
< 0.001) than the median IQR lowest SctO
2
value in patients in the LDP (66 62-69 %). More patients in the BCP group (57%) showed SctO
2
values ≤ 55% and/or a decrease of ≥ 20% from baseline (57%) compared with the LDP group (5% and 6%, respectively;
P
< 0.001 for each comparison).
Conclusions
More than 55% of patients undergoing arthroscopic shoulder surgery in the BCP experience cerebral desaturation events. In volunteers without anesthesia, no desaturation events were observed. The clinical importance of these findings needs further investigation.
In animal models of neuropathic pain (NP), promising results have been reported with the administration of minocycline, possibly through inhibition of spinal brain-derived neurotrophic factor (BDNF) ...expression. No data are available on the effect of amitriptyline and gabapentin on spinal BDNF expression. If the mechanism of action of the latter drugs does not involve brain-derived NP inhibition, further clinical research in BDNF is warranted.
In this placebo-controlled study, we investigated the effects of amitriptyline (5 mg/kg), gabapentin (50 mg/kg), and minocycline (25 mg/kg) twice a day on NP behavior in a sciatic chronic constriction injury (CCI) rat model. Drug treatment started 7 days after CCI and lasted 14 days. At postoperative day 21, spinal BDNF expression in laminae I and II was quantified using immunocytochemistry.
Sciatic CCI resulted in NP behavior throughout the duration of the experiment in the placebo group. When administered for 2 weeks, minocycline (P ≤ 0.001) and amitriptyline (P ≤ 0.05), but not gabapentin, reduced thermal hyperalgesia. None of these drugs reduced mechanical allodynia. As opposed to amitriptyline and gabapentin, 2 weeks of treatment with minocycline reduced brain-derived, neurotrophic factor immunoreactivity (P ≤ 0.05) in the ipsilateral dorsal horn.
Minocycline and amitriptyline both reduce NP behavior in a sciatic CCI rat model, but only minocycline reduces spinal BDNF, indicating different modes of action of these 2 drugs. The observed actions of minocycline closely fit the clinical needs for the treatment of NP.
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