REVIEW | doi:10.20944/preprints202007.0568.v1
Subject: Medicine & Pharmacology, Anesthesiology Keywords: SARS-CoV-2; COVID-19; respiratory failure; ARDS; ventilation; MODS; ECMO
Online: 24 July 2020 (04:00:50 CEST)
The Coronavirus Disease 2019 (COVID-19) pandemic has resulted in a significant surge of critically ill patients and an unprecedented demand on intensive care services. The rapidly evolving understanding of pathogenesis, limited disease specific evidence and demand-resource imbalances have posed significant challenges for intensive care clinicians. COVID-19 is a complex multisystem inflammatory vasculopathy with a significant mortality implication for those admitted to intensive care. Institutional strategic preparation and meticulous intensive care support are essential to maximising outcomes during the pandemic. The significant mortality variation observed between institutions and internationally, despite a single aetiology and uniform presentation, highlights the potential influence of management strategies on outcome. Given that optimal organ support and adjunctive therapies for COVID-19 have not yet been well defined by trial-based outcomes, strategies are predicated on existing literature and experiential learning. This review outlines the relevant pathophysiology and management strategies for critically ill patients with COVID-19, and shares some of the collective learning accumulated in a high volume Severe Respiratory Failure centre in London.
Sun, 19 July 2020
REVIEW | doi:10.20944/preprints202007.0426.v1
Subject: Medicine & Pharmacology, Anesthesiology Keywords: COVID-19; ARDS; Adenosine; CT-scan; Cytokines Storm
Online: 19 July 2020 (19:31:13 CEST)
Some COVID-19 patients develop interstitial pneumonia that can evolve into Acute Respiratory Distress Syndrome (ARDS). This is accompanied by an inflammatory cytokine storm. SarS-CoV has proteins capable of promoting cytokine storm, especially in patients with comorbidities, including obesity. Since there is currently no resolutive therapy for ARDS and given the scientific literature regarding the use of adenosine, its application has been hypothesized. Adenosine through its receptors is able to inhibit the acute inflammatory process, increase the protection capacity of the epithelial barrier and reduce the damage due to an overactivation of the immune system, such as in cytokine storms. These features are known in ischemia / reperfusion models and could also be exploited in acute lung injury, with hypoxia. In light of these hypotheses, for compassionate use, a COVID-19 patient, with unresponsive respiratory failure, was treated with adenosine. The results showed a rapid and clear improvement in clinical conditions, with the negative effect of detection of SarS-CoV2.
Thu, 4 June 2020
ARTICLE | doi:10.20944/preprints202006.0029.v1
Online: 4 June 2020 (08:03:48 CEST)
On the 9th March 2020, the first patient with COVID-19 was admitted to ICU in the Royal Gwent Hospital, Newport, Wales. We prospectively recorded the rate of ICU admissions of 52 patients with COVID-19 over 60 days, focusing on the epidemiology of ethnicity and deprivation. Patients were 65% (34 of 52) male and had a median (IQR) age of 55 (48-62) years. Prevalent comorbidities included obesity (52%); diabetes (33%), and asthma (23%). COVID-19 hospital and ICU inpatient numbers peaked on days 23 and 39, respectively – a lag of 16 days. The ICU mortality rate was 33% (17 of 52). Black, Asian and Minority Ethnics (BAME) population represented 35% of ICU COVID-19 admissions (18 of 52) and 35% of deaths (6 of 17). Within the BAME group, 72% (13 of 18) were found to reside in geographical areas representing the 20% most deprived in Wales, versus 27% of Caucasians (9 of 33). Less than 5% of the population within the hospital catchment area are of BAME descent, yet they represent a disproportionately high proportion of patients with ICU admission and mortality suffering from COVID-19. The interplay between ethnicity and deprivation, which is complex, may be a factor in our findings. This in turn could be related to an increased prevalence of co-morbidities; higher community exposure; or genetic polymorphisms.
Sat, 23 May 2020
CONCEPT PAPER | doi:10.20944/preprints202005.0373.v1
Subject: Medicine & Pharmacology, Anesthesiology Keywords: COVID-19; proteolytic cascades; thrombosis; viral sepsis
Online: 23 May 2020 (10:42:38 CEST)
Based on Chinese CDCP report on COVID-19, 14% of patients presented severe disease and 5% critical conditions. The average case-fatality rate was 2.3%, but mortality was as high as 49% in patients with critical illness. Serious life threatening thromboembolic complications have been found in 71·4% of non-survivors and micro/macro angiopathic coagulopathy has been found, also at autopsy, with highly increased neutrophil number, fibrinogen, concentrations of D-dimer and FDPs and NETs, ATIII decrease and normal number of platelets. A cytokine storm and interaction between inflammation and coagulation has been advocated as explanation of hypercoagulability. In this paper, it’s hypothesised that SARS-CoV-2 infection of alveolar cells induces recruitment of innate responder neutrophils, which release proteases and NETs inducing endothelial damage/endotheliopathy and imbalance of the four major proteolytic cascades (coagulation, complement, fibrinolysis and kallikrein) with prevalence of activators over inhibitors and consequent thrombotic complications. Platelets adhesion to damaged endothelium and the presence of ULVWF multimers, due to decreased ADAMTS13, contributes to the state of hypercoagulability. Neutrophil innate “unfriendly fire” response can be identified as the trigger of a “proteolytic storm”, responsible for subsequent well known prothrombotic condition and “cytokine storm”. The hypothesis explains also the pathology of recently described systemic “Kawasaki Disease like” vasculitis cases in Covid-19 young ill patients.
Tue, 7 April 2020
Subject: Medicine & Pharmacology, Anesthesiology Keywords: Covid-19; airway extubation; aerosols; laryngeal masks; occupational health
Online: 7 April 2020 (12:33:07 CEST)
We report smooth weaning from mechanical ventilation in a patient with COVID-19. The use of the supraglottic airway device can cause fewer coughs in weaning from mechanical ventilation. This procedure avoids the aerosol-generating procedure, tracheal extubation, and is beneficial in terms of occupational health for health care workers.
Sat, 7 March 2020
ARTICLE | doi:10.20944/preprints202003.0116.v1
Subject: Medicine & Pharmacology, Anesthesiology Keywords: continuous epidural infusion; dexamethasone; dexamethasone pulse therapy; inflammation; local anesthetics; neuropathic pain; postherpetic neuralgia
Online: 7 March 2020 (03:22:47 CET)
The most common complication of herpes zoster is postherpetic neuralgia (PHN), which is accompanied by severe pain that lowers patients’ quality of life. Although epidural injection of local anesthetics and steroids is effective in controlling neuropathic pain resulting from herpes zoster, few studies report the efficacy and safety of epidural steroid administration in PHN patients. We randomly assigned 42 patients with severe PHN pain (visual analog scale (VAS) score ≥7) to receive continuous epidural infusion of local anesthetics with either a one-time bolus of 5 mg dexamethasone or dexamethasone pulse therapy. VAS scores significantly decreased over time for all patients, but the reduction in VAS scores and likelihood of achieving complete remission were significantly greater among patients who received dexamethasone pulse therapy, without any adverse effects. These results show that continuous epidural infusion of local anesthetics with dexamethasone is effective and safe for reducing PHN pain and promoting complete remission and that more pronounced beneficial effects are associated with more intense epidural steroid administration.
Mon, 2 March 2020
REVIEW | doi:10.20944/preprints202003.0020.v1
Subject: Medicine & Pharmacology, Anesthesiology Keywords: visual patient; patient monitoring; avatar-based technology; situation awareness; user-centered design
Online: 2 March 2020 (00:56:03 CET)
Visual Patient technology is a situation awareness–oriented visualization technology that translates numerical and waveform patient monitoring data into a new user-centered visual language. Vital sign values are converted into colors, shapes, and rhythmic movements—a language humans can easily perceive and interpret—on a patient avatar model in real time. In this review, we summarize the current state of the research on the Visual Patient, including the technology, its history, and its scientific context. We also provide a summary of our primary research and a brief overview of research work on similar user-centered visualizations in medicine. In several computer-based studies under various experimental conditions, Visual Patient transferred more information per unit time, increased perceived diagnostic certainty, and lowered perceived workload. Eye tracking showed the technology worked because of the way it synthesizes and transforms vital sign information into new and logical forms corresponding to the real phenomena. The technology could be particularly useful for improving situation awareness in settings with high cognitive demand or when users must make quick decisions. This comprehensive review of Visual Patient research is the foundation for an evaluation of the technology in clinical applications, starting with a high-fidelity simulation study in early 2020.
Tue, 25 February 2020
Subject: Medicine & Pharmacology, Anesthesiology Keywords: effective anesthesia; earthquake; orthopedic; victim’s management
Online: 25 February 2020 (12:14:03 CET)
Lombok earthquake that occurred in July 2018 has three large magnitude earthquakes that caused huge losses; 564 victims died, 1684 injured, 445 343 refugees, and 215 628 houses were damaged. The role of anesthesiology is very important to give prompt therapy for injured victims. This research gave an overview of the important role of Anesthesiologist and the selection of anesthesia techniques during the natural disasters’ victims’ management. This study was conducted by collecting data of all earthquake victims treated at the emergency room (ER) of RSUD NTB on August 6th and 7th 2018 and all victims operated during August 5 – 25th 2018. All data were recorded, analyzed, and presented in descriptive form using frequency, pie chart, and bar diagrams. The result shown that the highest number of patients treated in ER are during the first seven days after the earthquake and reduced to several weeks. The majority of patients treated are trauma patients who need orthopedic surgery. Since limited number of anesthesiologist should be considered with the right selection of anesthesia techniques, so that the disaster preparedness could be prepared well and the disaster management could run well. General anesthesia was widely used than regional anesthesia, but the different is not significant. The type of regional anesthetic drug usually used is lidodex in combination with catapres. The role of anesthesiologist during disaster is important to handle a safe and optimal surgical condition.
Fri, 14 February 2020
ARTICLE | doi:10.20944/preprints202002.0186.v1
Subject: Medicine & Pharmacology, Anesthesiology Keywords: breakthrough cancer pain; cancer-associated pain; cancer; health-related quality of life; sleep disorders; transmucosal fentanyl
Online: 14 February 2020 (03:36:53 CET)
Objectives: To explore the effect of breakthrough cancer pain (BTcP) treatment on quality of sleep and other aspects of the health-related quality of life (HRQoL) in patients with cancer pain. Methods: In an observational, multicenter, cohort study, cancer patients from palliative care units, oncology departments, and pain clinics and affected by BTcP were included. Enrolled patients were assessed at the four visits: T0 (baseline), T7, T14, and T28. Well-controlled chronic background pain during the whole study period was mandatory. BTcP was treated through transmucosal fentanyl. Three questionnaires were used to measure the HRQoL: EORTC QLQ-C15-PAL, Pittsburgh Sleep Quality Index (PSQI), and the Edmonton Symptom Assessment System (ESAS). Results: In 154 patients, the HRQoL showed a significant improvement for all physical and emotional characteristics in the EORTC QLQ-C15-PAL, except for nausea and vomiting (Linear p-value = 0.1) and dyspnoea (Linear p-value =0.05). The ESAS and PSQI questionnaires confirmed these positive results (p<0.0001 and p=0.002, respectively). Conclusions: This prospective investigation by an Italian expert group, has confirmed that careful management of BTcP induces a paramount improvement on the HRQoL. Because in cancer patients there is a high prevalence of BTcP and this severe acute pain has deleterious consequences, this information can have an important clinical significance
Mon, 10 February 2020
ARTICLE | doi:10.20944/preprints202002.0130.v1
Subject: Medicine & Pharmacology, Anesthesiology Keywords: state entropy; response entropy; general anaesthesia; patient safety; recovery.
Online: 10 February 2020 (15:24:34 CET)
Study background and aims: Laparoscopic cholecystectomy is one of the most frequently performed interventions in departments of general surgery. One of the most important aims in achieving perioperative stability of these patients is diminishing the impact of general anesthesia on the hemodynamic stability and the optimization of anesthetic drug doses based on the individual clinical profile of each patient. The objective of this study is the evaluation of the impact monitoring the depth of anesthesia through Entropy (state entropy – SE and response entropy -RE) has on the hemodynamic stability and on the doses of volatile anesthetic. Material and Methods: This is a prospective, observational, randomized, monocentric study carried out between January 2019 and December 2019 in the Clinic of Anesthesia and Intensive Care from the “Pius Brînzeu” Emergency County Hospital in Timișoara, Romania. The patients included in the study were divided in two study groups; patients in Group A (target group) received multimodal monitoring that included monitoring of standard parameters and of Entropy (SE and RE), while patients in Group B (control group) only received standard monitoring. Anesthetic dose in group A were optimized to achieve a target entropy of 40-60. Results: 68 patients met the inclusion criteria and were allocated to one of the two study groups, Group A (N=43) and Group B (N=25). There were no statistically significant differences identified between the two groups for both demographical and clinical data (p>0.05). Statistically significant differences have been identified for the number of hypotensive episodes (p = 0.011, 95% CI 0.1851 to 0.7042) and for the number of episodes of bradycardia (p < 0.0001, 95% CI 0.3296 to 0.7923). Moreover, there was a significant difference in the Sevoflurane consumption between the two study groups (p = 0.0498, 95% CI -0.3942 to 0.9047). Conclusions: The implementation of the multimodal monitoring protocol that includes the standard parameters and the measurement of Entropy for determining the depth of anesthesia (SE and RE) lead to a considerable improvement in perioperative hemodynamic stability. Optimizing the doses of anesthetic drugs based on the individual clinical profile of each patient leads to a considerable decrease in drug consumption as well as to a lower incidence of hemodynamic side-effects.
Fri, 7 February 2020
ARTICLE | doi:10.20944/preprints202002.0093.v1
Subject: Medicine & Pharmacology, Anesthesiology Keywords: Ketamine; Paravertebral block; Posterolateral thoracotomy; Thoracotomy; Visual analog scale
Online: 7 February 2020 (09:28:16 CET)
Severe postoperative pain affects most patients after thoracotomy and is a risk factor for post-thoracotomy pain syndrome (PTPS). This randomized controlled trial compared preemptively administered ketamine versus paravertebral block (PVB) versus control in patients undergoing posterolateral thoracotomy. The primary outcome was acute pain intensity on the visual analog scale (VAS) on the first postoperative day. Secondary outcomes included morphine consumption, patient satisfaction, and PTPS assessment with Neuropathic Pain Syndrome Inventory (NPSI). Acute pain intensity was significantly lower with PVB compared to other groups at four out of six time points. Patients in the PVB group used significantly less morphine via a patient-controlled analgesia pump than participants in other groups. Moreover, patients were more satisfied with postoperative pain management after PVB. PVB, but not ketamine, decreased PTPS intensity at 1, 3, and 6 months after posterolateral thoracotomy. Acute pain intensity at hour 8 and PTPS intensity at month 3 correlated positively with PTPS at month 6. Bodyweight was negatively associated with chronic pain at month 6. Thus, PVB but not preemptively administered ketamine decreases both acute and chronic pain intensity following posterolateral thoracotomies. The trial was prospectively registered at the Australian New Zealand Clinical Trial Registry (https://www.anzctr.org.au/; ACTRN12616000900415; 07 July 2016).
Sun, 29 December 2019
ARTICLE | doi:10.20944/preprints201912.0378.v1
Subject: Medicine & Pharmacology, Anesthesiology Keywords: blood viscosity; transit-time flow measurement; coronary artery bypass surgery
Online: 29 December 2019 (10:22:23 CET)
Background: Transit-time flow measurement (TTFM) is frequently used to evaluate intraoperative quality control during coronary artery bypass grafting (CABG). Although TTFM has the ability to assess graft failure intraoperatively, the perioperative factors affecting TTFM during CABG surgery remain poorly understood. Methods: Patients who underwent CABG surgery at a single institution between July 2016 and May 2018 were prospectively evaluated. Patients’ demographic characteristics, previous medical history, Euroscore, the results of preoperative blood tests, and intraoperative data were recorded. TTFM and blood viscosity were measured hemodynamically, and mean flow (mL/min) and pulsatility index (PI) were recorded. Arterial blood gas was analyzed immediately after anastomosis of the left internal mammary artery (LIMA) to the left descending artery (LAD) and before sternal closure. Factors associated with TTFM were assessed by multiple linear regression analysis. Results: Of the 62 patients who underwent CABG surgery during the study period, 57 were evaluated, including 49 who underwent off-pump and eight who underwent on-pump surgery. Blood viscosity was not significantly associated with TTFM (p > 0.05). However, TTFM was significantly associated with body mass index (BMI), systolic blood pressure, and cardiac index (p < 0.05 each). Conclusions: Blood viscosity was not significantly associated with intraoperative graft flow. Blood flow of graft vessels, however, was significantly associated with BMI, systolic blood pressure, and cardiac index.
Sun, 10 November 2019
ARTICLE | doi:10.20944/preprints201911.0101.v1
Subject: Medicine & Pharmacology, Anesthesiology Keywords: chronic pain; epigenetics; neuropathic pain; postoperative pain; thoracic surgery; video-assisted
Online: 10 November 2019 (09:29:13 CET)
Background: Elucidation of epigenetic mechanisms correlating with neuropathic pain in humans is crucial for the prevention and treatment of this treatment-resistant pain state. In the present study, associations between neuropathic pain characteristics and DNA methylation of the transient receptor potential ankyrin 1(TRPA1) gene were evaluated in chronic pain patients and preoperative patients. Methods: Pain and psychological states were prospectively assessed in patients who suffered chronic pain or were scheduled for thoracic surgery. Neuropathic characteristics were assessed using the Douleur Neuropathique 4 (DN4) questionnaire. DNA methylation levels of the CpG island in the TRPA1 gene were examined using whole blood. Results: Forty-eight adult patients were enrolled in this study. Increases in DNA methylation rates at CpG -51 showed positive correlations with increases in the DN4 score both in preoperative and chronic pain patients. Combined methylation rates at CpG -51 also significantly increased together with increase in DN4 scores. Conclusions: Neuropathic pain characteristics are likely associated with methylation rates at the promoter region of the TRPA1 gene in human peripheral blood.
Sun, 29 September 2019
ARTICLE | doi:10.20944/preprints201909.0330.v1
Subject: Medicine & Pharmacology, Anesthesiology Keywords: myocardial injury after non-cardiac surgery; anesthetic technique; high-sensitivity troponin i
Online: 29 September 2019 (07:08:24 CEST)
The cardioprotective effects of volatile anesthetics versus total intravenous anesthesia (TIVA) are controversial, especially in patients undergoing non-cardiac surgery. Using current generation high-sensitivity cardiac troponin (hs-cTn), we aimed to evaluate the effect of anesthetics on the occurrence of myocardial injury after non-cardiac surgery (MINS). From February 2010 to December 2016, 3555 patients without preoperative hs-cTn elevation underwent non-cardiac surgery under general anesthesia. Patients were grouped according to anesthetic agent; 659 patients were classified into a propofol-remifentanil total intravenous anesthesia (TIVA) group, and 2896 patients were classified into into a volatile group. To balance the use of remifentanil between groups, a balanced group (n=1622) was generated with patients who received remifentanil infusion in the volatile group, and two separate comparisons were performed (TIVA vs. volatile and TIVA vs. balanced). The primary outcome was occurrence of MINS, defined as rise of hs-cTn I ≥ 0.04 ng/mL within postoperative 48 hours. The secondary outcomes were 30-day mortality, postoperative acute kidney injury (AKI), and adverse events during hospital stay (mortality, type I myocardial infarction (MI), and new-onset arrhythmia). In propensity-matched analyses, the occurrence of MINS was lower in the TIVA group compared to the volatile group (OR 0.642; 95% CI 0.450-0.914; p = 0.014). However, after balancing the use of remifentanil, there was no difference between groups in the risk of MINS (OR 0.832; 95% CI 0.554-1.251; p-value = 0.377). There were no significant associations between the two groups in type 1 MI, new-onset atrial fibrillation, in-hospital and 30-day mortality before and after balancing the use of remifentanil. However, the incidence of postoperative AKI was lower in the TIVA group (OR 0.362; 95% CI 0.194-0.675; p-value = 0.001). After balancing the use of remifentanil, volatile anesthesia and TIVA showed comparable effects on MINS in patients undergoing non-cardiac surgery without preoperative myocardial injury. Further studies are needed on the benefit of remifentanil infusion.
Tue, 2 April 2019
ARTICLE | doi:10.20944/preprints201904.0030.v1
Subject: Medicine & Pharmacology, Anesthesiology Keywords: Brody effect; electrocardiographic variation; R-wave amplitude; hemodynamic monitoring; pulse pressure variation
Online: 2 April 2019 (12:19:31 CEST)
The aim of this study was to analyze whether the respiratory variation in ECG standard lead II R-wave amplitude (ΔRDII) could be used to assess intravascular volume status following inferior vena cava (IVC) clamping. This clamping causes an acute decrease in cardiac output during liver transplantation (LT). We retrospectively compared ΔRDII and related variables before and after IVC clamping in 34 recipients. Receiver operating characteristic (ROC) curve and area under the curve (AUC) analyses were used to derive a cutoff value of ΔRDII for predicting pulse pressure variation (PPV). After IVC clamping, cardiac output significantly decreased while ΔRDII significantly increased (P = 0.002). The cutoff value of ΔRDII for predicting a PPV >13% was 16.9% (AUC: 0.685) with a sensitivity of 57.9% and specificity of 77.6% (95% confidence interval 0.561 – 0.793, P = 0.015). Frequency analysis of ECG also significantly increased in the respiratory frequency band (P = 0.016). Although significant changes in ΔRDII during vena cava clamping were found at norepinephrine doses < 0.1 μg/kg/min (P = 0.014), such changes were not significant at norepinephrine doses > 0.1 μg/kg/minP = 0.093). ΔRDII could be a noninvasive dynamic parameter in LT recipients presenting with hemodynamic fluctuation. Based on our data, we recommended cautious interpretation of ΔRDII may be requisite according to vasopressor administration status.
Thu, 8 November 2018
ARTICLE | doi:10.20944/preprints201811.0005.v1
Subject: Medicine & Pharmacology, Anesthesiology Keywords: anaesthesia, general; anaesthesia recovery period; single dose of rocuronium; sugammadex; neostigmine
Online: 8 November 2018 (14:00:01 CET)
There is a lack of data comparing sugammadex with anticholinesterase for the quality of anaesthesia recovery, especially following a single bolus dose of rocuronium. Thus, we evaluated the influence of reversal with sugammadex or neostigmine on post-operative quality of recovery by using the Post-operative Quality Recovery Scale (PQRS). A total of 86 patients undergoing trans-pars plana vitrectomy (TPPV) under general anaesthesia were intubated following a single bolus dose of rocuronium (0.6 mg/kg). At the end of surgery, patients were received either neostigmine or sugammadex. The quality of recovery was assessed using the PQRS at 15 minutes and 40 minutes after surgery, and on post-operative day 1. The recovery rate in the physiological domain was higher in the sugammadex group at 15 minutes after surgery (P = 0.02). Though there were no significant differences in the overall cognitive recovery domain, patients in the sugammadex group could recall more numbers in reverse order. However, there were no significant differences between the groups in the other domains of the PQRS. The use of sugammadex may increase the quality of the post-operative physiological recovery at early post-operative periods compared with neostigmine use following a single bolus dose of rocuronium in patients undergoing TPPV with general anaesthesia.
Fri, 8 June 2018
REVIEW | doi:10.20944/preprints201806.0134.v1
Subject: Medicine & Pharmacology, Anesthesiology Keywords: chronic pediatric pain; low income country; middle income country; low and middle income country; pediatric palliative care.
Online: 8 June 2018 (12:45:24 CEST)
Chronic pain is a serious health concern and potentially debilitating condition, leading to anxiety, depression, reduced productivity and functionality, and poor quality of life. This condition can be even more detrimental and incapacitating in the pediatric patient population. In low and middle income countries (LMICs), pain services are inadequate or unavailable, leaving most of the world's pediatric population with chronic pain untreated. Many of these children in LMICs are suffering without treatment, and often die in pain. Awareness and advocacy for this population must be prioritized. We reviewed the available literature on the chronic pediatric pain burden in LMICs, barriers to treatments, and current efforts to treat these patients.
Wed, 6 June 2018
ARTICLE | doi:10.20944/preprints201806.0083.v1
Subject: Medicine & Pharmacology, Anesthesiology Keywords: anesthesia; neurotoxicity; synapse; mTOR; neurodevelopment
Online: 6 June 2018 (10:36:51 CEST)
Human epidemiologic studies and laboratory investigations in animal models suggest that exposure to general anesthetic agents (GAs) have harmful effects on brain development. The mechanism underlying this putative iatrogenic condition is not clear and there are currently no accepted strategies for prophylaxis or treatment. Recent evidence suggests that anesthetics might cause persistent deficits in synaptogenesis by disrupting key events in neurodevelopment. Using an in vitro model consisting of dissociated primary cultured mouse neurons we demonstrate abnormal pre- and post-synaptic marker expression after a clinically relevant isoflurane anesthesia exposure conducted during neuron development. We find that pharmacologic inhibition of the mechanistic target of rapamycin (mTOR) pathway can reverse the observed changes. Isoflurane exposure increases expression of phospho-S6, a marker of mTOR pathway activity, in a concentration-dependent fashion and this effect occurs throughout neuronal development. The mTOR 1 complex (mTORC1) and the mTOR 2 complex (mTORC2) branches of the pathway are both activated by isoflurane exposure and this is reversible with branch-specific inhibitors. Upregulation of mTOR is also seen with sevoflurane and propofol exposure, suggesting that this mechanism of developmental anesthetic neurotoxicity may occur with all the commonly used GAs in pediatric practice. We conclude that GAs disrupt the development of neurons during development by activating a well-defined neurodevelopmental disease pathway and that this phenotype can be reversed by pharmacologic inhibition.
Fri, 25 May 2018
ARTICLE | doi:10.20944/preprints201805.0364.v1
Subject: Medicine & Pharmacology, Anesthesiology Keywords: ultrasonography; preoperative; postoperative; collabsibility index; inferior vena cava diameter
Online: 25 May 2018 (11:42:21 CEST)
Background: Ultrasound measurement of dynamic changes in inferior vena cava (IVC) diameter and collapsibility index (CI) evaluates to estimate the fluid responsiveness and intravascular volume status. We conducted a analysis to quantify the sonographic measurement of IVC diameter changes in adult patients at preoperative and postoperative period. Methods: Ultrasonography was performed on 72 patients scheduled for surgery with American Society of Anesthesiologists physical status I to III. Quantitative assessments of the end-expiration (Dmin), end-inspiration (Dmax) and CI at preoperative and postoperative period were compared in a prospective, observational study. The patients received intravenous fluid according to standard protocol regimes peroperatively. The cutt-off value of dIVC 40% was accepted as hypovolemia. Results: Ultrasonography of IVC measurement was unsuccessful in 12.5% of patients and 63 patients remained for analyses. The mean age was 43.29 ± 17.22 (range 18 - 86) years. The average diameter of the Dmin, Dmax and dIVC at preoperative and postoperative were 1.99 ± 0.31 vs. 2.05 ± 0.29 cm, 1.72 ± 0.33 vs. 1.74 ± 0.32 cm, 14.0 ± 9.60 % vs. 15.14 ± 11.18 %, respectively (p<0.05). Using a threshold dIVC of 40%, one patient preoperatively and 5 postoperatively were hypovolemic (p<0.05). CI was also positively associated preoperatively and postoperatively (regression coefficient = 0.438, p<0.01). Conclusion: The diameter of IVC did not change preoperatively and postoperatively in adult patients with standard fluid regimens. The parameters of the IVC diameter increased postoperatively according to preoperative period.
Mon, 25 December 2017
REVIEW | doi:10.20944/preprints201712.0172.v1
Subject: Medicine & Pharmacology, Anesthesiology Keywords: palliative care team; seriously ill patients; end-of-life; quality of life; symptom relief; acute palliative care unit; cost savings
Online: 25 December 2017 (08:50:18 CET)
Traditionally, palliative care (PC) systems focused on the needs of advanced cancer patients. But, most patients needing PC have end-stage organ diseases. Similarly, PC models focused on the needs of patients in hospice or at home; however, in most cases PC is provided in acute hospitals. Indeed, the symptom burden that these patients experience in the last year of life frequently forces them to seek care in Emergency Department. The majority of them are admitted to the hospital and many die. This issue poses important concerns. Despite the efforts of attending healthcare professionals, inhospital patients do not receive optimal care near the end-of-life. Also, evidence is emerging that delay in identifying patients needing PC have a detrimental impact on their quality of life (QoL). Therefore, there is an urgent need to early and properly identify these patients among those hospitalized. Several trials reported the efficacy of PC in improving the QoL in these patients. Each hospital should ensure that a multidisciplinary PC team is available to support attending physicians to achieve the best QoL for both PC patients and their families. This review discusses the role and the impact of inhospital PC in patients with end-stage disease or advanced cancer.
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