Evaluation of the quality of cardiopulmonary resuscitation provided by the emergency response team at a tertiary care hospital.

Background and Aims: Chest compression fraction is the proportion of time spent on chest compression during cardiopulmonary resuscitation (CPR). The aims of this study were to know the quality of CPR provided during in-hospital cardiac arrest (IHCA) by analysing the chest compression fraction and to see the correlation of chest compression fraction with return of spontaneous circulation (ROSC) in the hospital setting. Methods: This prospective observational study was conducted in patients aged >18 years who developed IHCA. An observer would assess the quality of CPR provided by noting the time spent on chest compression. The chest compression fraction was calculated and correlated in patients with ROSC and without ROSC. Patients who survived were followed until discharge, and their neurological score was determined using the cerebral performance category (CPC). Results: We included 126 patients in the study; the mean chest compression fraction achieved was 78% (standard deviation [SD] ± 5). A total of 73 (58%) patients achieved ROSC and among them, 11 patients (9%) survived to hospital discharge. We found that the patients with ROSC had a significantly higher chest compression fraction of 80% (SD ± 5), as compared to 75% (SD ± 5), in whom ROSC could not be achieved. A multivariate logistic regression test showed higher odds (1.125) of ROSC in patients with high chest compression fraction. The mean CPC among the survivors was 1.4 (SD ± 0.5). Conclusion: Our study shows that health-care providers in our hospital provide high-quality CPR, and chest compression fraction is independently associated with ROSC in IHCA.

Changes in stroke volume variation and cardiac index during open major bowel surgery.

BACKGROUND: Stroke volume variation (SVV) is a dynamic indicator of preload, which is a determinant of cardiac output. Aims: Aim of this study was to evaluate the relationship between changes in SVV and cardiac index (CI) in patients with normal left ventricular function undergoing major open abdominal surgery. PATIENTS AND METHODS: Patients undergoing major open abdominal surgery were monitored continuously with FloTrac® to measure SVV and CI along with standard monitoring. Both SVV and CI were noted at baseline and every 10 min thereafter till the end of surgery and were observed for concurrence between the measurements. RESULTS: 1800 pairs of measurement of SVV and CI were obtained from 60 patients. Mean SVV and CI (of all patients) measured at different time points of measurement showed that as SVV increased with time, the CI dropped correspondingly. When individual readings of CI and SVV were plotted against each other, the scatter was found to be wide, reiterating the lack of agreement between the two parameters (R2 = 0.035). SVV >13% suggesting hypovolemia was found at 207 time points. Of these, 175 had a CI >2.5 L/min/m2 and only 32 patients had a CI <2.5 L/min/m2. CONCLUSION: SVV, a dynamic index of fluid responsiveness can be used to monitor patients expected to have large fluid shifts during major abdominal surgery. It is very specific and has a high negative predictive value. When SVV increases, CI is usually maintained. Since many factors affect SVV and CI, any increase in SVV >13%, must be correlated with other parameters before administration of the fluid challenge.

Goal-Directed vs Traditional Approach to Intraoperative Fluid Therapy during Open Major Bowel Surgery: Is There a Difference?

INTRODUCTION: Optimum perioperative fluid therapy is important to improve the outcome of the surgical patient. This study prospectively compared goal-directed intraoperative fluid therapy with traditional fluid therapy in general surgical patients undergoing open major bowel surgery. METHODOLOGY: Patients between 20 and 70 years of age, either gender, ASA I and II, and scheduled for elective open major bowel surgery were included in the study. Patients who underwent laparoscopic and other surgeries were excluded. After routine induction of general anaesthesia, the patients were randomised to either the control group (traditional fluid therapy), the FloTrac group (based on stroke volume variation), or the PVI group (based on pleth variability index). Fluid input and output, recovery characteristics, and complications were noted. RESULTS: 306 patients, with 102 in each group, were enrolled. Five patients (control (1), FloTrac (2), and PVI (2)) were inoperable and were excluded. Demographic data, ASA PS, anaesthetic technique, duration of surgery, and surgical procedures were comparable. The control group received significantly more crystalloids (3200 ml) than the FloTrac (2000 ml) and PVI groups (1875 ml), whereas infusion of colloids was higher in the FloTrac (400-700 ml) and PVI (200-500 ml) groups than in the control group (0-500 ml). The control group had significantly positive net fluid balance intraoperatively (2500 ml, 9 ml/kg/h) compared to the FloTrac (1515 ml, 5.4 ml/kg/h) and PVI (1420 ml, 6 ml/kg/h) groups. Days to ICU stay, HDU stay, return of bowel movement, oral intake, morbidity, duration of hospital stay, and survival rate were comparable. The total number of complications was not different between the three groups. Anastomotic leaks occurred more often in the Control group than in the others, but the numbers were small. CONCLUSIONS: Use of goal-directed fluid management, either with FloTrac or pleth variability index results in a lower volume infusion and lower net fluid balance. However, the complication rate is similar to that of traditional fluid therapy. This trial is registered with CTRI/2018/04/013016.

Unrecognized blunt tracheal trauma with massive pneumomediastinum and tension pneumothorax.

Blunt neck trauma with an associated laryngotracheal injury is rare. We report a patient with blunt neck trauma who came to the emergency room and was sent to ward without realizing the seriousness of the situation. He presented later with respiratory distress and an anesthesiologist was called in for emergency airway management. Airway management in such a situation is described in this report.

Controlled comparison between betamethasone gel and lidocaine jelly applied over tracheal tube to reduce postoperative sore throat, cough, and hoarseness of voice.

BACKGROUND: Postoperative sore throat, cough, and hoarseness of voice though minor sequelae after general tracheal anaesthesia can be distressing to the patient. METHODS: This prospective, randomized, double blind, controlled study compares the incidence of postoperative sore throat, cough, and hoarseness of voice after general tracheal anaesthesia when applying betamethasone gel (betamethasone group) or lidocaine jelly (lidocaine group) on the tracheal tube. One hundred and fifty ASA class I and II patients undergoing elective surgeries under general orotracheal anaesthesia were randomized into three groups: betamethasone gel, lidocaine jelly, and control groups. In the post-anaesthesia care unit, a blinded anaesthesiologist interviewed all patients on postoperative sore throat, cough, and hoarseness of voice at 1, 6, 12, and 24 h after operation. RESULTS: In the first 24 h after surgery, the incidence of postoperative sore throat was 40, 100, and 100%; cough was 6, 40, and 28%; and hoarseness of voice was 4.1, 32.9, and 50%, for the betamethasone, lidocaine and control groups, respectively. The incidence of postoperative sore throat, cough, and hoarseness of voice was significantly lower in the betamethasone group compared with the other two groups (P<0.05). CONCLUSIONS: A wide spread application of betamethasone gel on the tracheal tube decreases the incidence and severity of postoperative sore throat, cough, and hoarseness of voice.

The effect of ephedrine on intubating conditions and haemodynamics during rapid tracheal intubation using propofol and rocuronium.

BACKGROUND: We compared the effect of pre-treatment with ephedrine 75, 100, 150 microg kg(-1) and saline on intubating conditions and haemodynamics during rapid tracheal intubation using propofol and rocuronium. METHODS: One hundred adult patients randomized into one of the four groups-PE 75, PE 100, PE 150, and saline (control) groups-were pre-treated with i.v. ephedrine 75, 100, 150 microg kg(-1) or saline, respectively, 1 min before rapid tracheal intubation using propofol 2.5 mg kg(-1) and rocuronium 0.6 mg kg(-1). A blinded anaesthesiologist assessed the intubating conditions. Heart rate and mean arterial pressure were recorded before anaesthesia induction (baseline), post-induction, and every minute after intubation for 5 min. A 20% change in haemodynamic variables from baseline was regarded as clinically significant. Data were analysed using anova test with post hoc Tukey's test and chi2 or Fisher's exact test. P < 0.05 was regarded as significant. RESULTS: Patient characteristics, baseline heart rate, and mean arterial pressure were comparable between the groups. Intubating conditions were significantly better in the PE 75 (P = 0.003) and PE 100 (P = 0.001) groups. A significant increase in heart rate was observed in the PE 75 and PE 150 groups when compared with the saline group. A statistically significant difference in mean arterial pressure was noted between PE 75 and PE 150 groups and between PE 150 and saline groups at most of the time intervals. However, when considering the clinical significance of these, all groups were comparable (P > 0.05). CONCLUSIONS: Ephedrine either 75 or 100 microg kg(-1) given before rapid tracheal intubation using propofol and rocuronium bromide improves the intubation conditions. It is not effective in preventing the hypotension which follows ensuing induction of anaesthesia.

Structural basis for antagonism by suramin of heparin binding to vaccinia complement protein.

Suramin is a competitive inhibitor of heparin binding to many proteins, including viral envelope proteins, protein tyrosine phosphatases, and fibroblast growth factors (FGFs). It has been clinically evaluated as a potential therapeutic in treatment of cancers caused by unregulated angiogenesis, triggered by FGFs. Although it has shown clinical promise in treatment of several cancers, suramin has many undesirable side effects. There is currently no experimental structure that reveals the molecular interactions responsible for suramin inhibition of heparin binding, which could be of potential use in structure-assisted design of improved analogues of suramin. We report the structure of suramin, in complex with the heparin-binding site of vaccinia virus complement control protein (VCP), which interacts with heparin in a geometrically similar manner to many FGFs. The larger than anticipated flexibility of suramin manifested in this structure, and other details of VCP-suramin interactions, might provide useful structural information for interpreting interactions of suramin with many proteins.

Modulation of the nucleoside triphosphatase/RNA helicase and 5'-RNA triphosphatase activities of Dengue virus type 2 nonstructural protein 3 (NS3) by interaction with NS5, the RNA-dependent RNA polymerase.

Dengue virus type 2 (DEN2), a member of the Flaviviridae family, is a re-emerging human pathogen of global significance. DEN2 nonstructural protein 3 (NS3) has a serine protease domain (NS3-pro) and requires the hydrophilic domain of NS2B (NS2BH) for activation. NS3 is also an RNA-stimulated nucleoside triphosphatase (NTPase)/RNA helicase and a 5'-RNA triphosphatase (RTPase). In this study the first biochemical and kinetic properties of full-length NS3 (NS3FL)-associated NTPase, RTPase, and RNA helicase are presented. The NS3FL showed an enhanced RNA helicase activity compared with the NS3-pro-minus NS3, which was further enhanced by the presence of the NS2BH (NS2BH-NS3FL). An active protease catalytic triad is not required for the stimulatory effect, suggesting that the overall folding of the N-terminal protease domain contributes to this enhancement. In DEN2-infected mammalian cells, NS3 and NS5, the viral 5'-RNA methyltransferase/polymerase, exist as a complex. Therefore, the effect of NS5 on the NS3 NTPase activity was examined. The results show that NS5 stimulated the NS3 NTPase and RTPase activities. The NS5 stimulation of NS3 NTPase was dose-dependent until an equimolar ratio was reached. Moreover, the conserved motif, 184RKRK, of NS3 played a crucial role in binding to RNA substrate and modulating the NTPase/RNA helicase and RTPase activities of NS3.

Yellow fever virus NS2B-NS3 protease: characterization of charged-to-alanine mutant and revertant viruses and analysis of polyprotein-cleavage activities.

A series of 46 charged-to-alanine mutations in the yellow fever virus NS2B-NS3 protease, previously characterized in cell-free and transient cellular expression systems, was tested for their effects on virus recovery. Four distinct plaque phenotypes were observed in cell culture: parental plaque-size (13 mutants), reduced plaque-size (17 mutants), small plaque-size (8 mutants) and no plaque-formation (8 mutants). No mutants displayed any temperature sensitivity based on recovery of virus after RNA transfection at 32 versus 37 degrees C. Most small plaque-mutants were defective in growth efficiency compared with parental virus. However not all small plaque-mutants had defective 2B/3 cleavage, with some showing selective defects at other non-structural protein cleavage sites. Revertant viruses were recovered for six mutations that caused reduced plaque sizes. Same-site and second-site mutations occurred in NS2B, and one second-site mutation occurred in the NS3 protease domain. Some reversion mutations ameliorated defects in cleavage activity and plaque size caused by the original mutation. These data indicate that certain mutations that reduce NS2B-NS3 protease cleavage activity cause growth restriction of yellow fever virus in cell culture. However, for at least two mutations, processing defects other than impaired cleavage activity at the 2B/3 site may account for the mutant phenotype. The existence of reversion mutations primarily in NS2B rather than NS3, suggests that the protease domain is less tolerant of structural perturbation compared with the NS2B protein.

Identification and characterization of nonsubstrate based inhibitors of the essential dengue and West Nile virus proteases.

The 72 known members of the flavivirus genus include lethal human pathogens such as Yellow Fever, West Nile, and Dengue viruses. There is at present no known chemotherapy for any flavivirus and no effective vaccines for most. A common genomic organization and molecular mechanisms of replication in hosts are shared by flaviviruses with a viral serine protease playing a pivotal role in processing the viral polyprotein into component polypeptides, an obligatory step in viral replication. Using the structure of the dengue serine protease complexed with a protein inhibitor as a template, we have identified five compounds, which inhibit the enzyme. We also describe parallel inhibitory activity of these compounds against the West Nile virus Protease. A few of the compounds appear to provide a template for design of more potent and specific inhibitors of the dengue and West Nile virus proteases. Sequence similarities among flaviviral proteases suggests that such compounds might also possibly inhibit other flaviviral proteases.

Structure of vaccinia complement protein in complex with heparin and potential implications for complement regulation.

Vaccinia virus complement control protein (VCP), a homolog of the regulators of the complement activation family of proteins, inhibits complement activation through mechanisms similar to human fluid-phase complement regulators factor H and C4b-binding protein. VCP has a heparin-binding activity that assists vaccinia in host interactions. Interaction with cell-surface polyanions like heparin is centrally important in the functioning of fluid-phase complement regulators and is the basis of host-target discrimination by the alternative pathway. We report the structure of VCP in complex with a heparin decasaccharide, which reveals changes in VCP that might be pertinent to complement regulation. Properties that VCP shares with fluid-phase complement regulators suggest that such conformational changes may be of relevance in the functioning of other complement regulators. Additionally, comparison of VCP-heparin interactions with potentially similar interactions in factor H might enable understanding of the structural basis of familial hemolytic uremic syndrome, attributed to mutational disruption of heparin and C3b binding by factor H.

Vaccinia virus complement control protein is monomeric, and retains structural and functional integrity after exposure to adverse conditions.

Vaccinia virus complement control protein (VCP) possesses the ability to inhibit both classical and alternative pathways of complement activation, as well as bind to heparin or heparan sulfate proteoglycans, making it a unique multifunctional protein with therapeutic potential. Recently, the structure of the complete molecule of VCP was determined by X-ray crystallography. Two or three VCP molecules were packed within the unit cells of both crystal forms. Using gel filtration, VCP has now been shown to exist as a monomer in solution. To test the stability of this molecule, VCP was studied by nuclear magnetic resonance (NMR) over a range of temperatures and by differential scanning calorimetry (DSC). It was also subjected to adverse physical conditions, including, freeze-thawing, changes in pH, changes in temperature, and storage at room temperature. VCP melts fully reversibly, and it maintained its 3-D structure and the ability to inhibit serum-induced hemolysis of sheep red blood cells after exposure to many extreme conditions. The robustness of VCP may be rationalized in terms of its architecture.