Ulinastatin Add-on to Standard of Care in Critically Ill COVID-19 Patients: A Multicenter, Retrospective Study

Aim: To assess the impact on 30-day mortality with ulinastatin (ULI) used as add-on to standard of care (SOC) compared to SOC alone in coronavirus disease (COVID-19) patients requiring admission to the intensive care unit (ICU). Materials and methods: In this multicentric, retrospective study, we collected data on clinical, laboratory, and outcome parameters in patients with COVID-19. Thirty-day mortality outcome was compared among patients treated with SOC alone and ULI used as add-on to SOC. Odds ratio (OR) and 95% confidence intervals (CI) were determined to identify the predictors of 30-day mortality. Results: Ninety-four patients were identified and enrolled in both groups with comparable baseline parameters. On univariate analysis, 30-day mortality was significantly lower in ULI plus SOC group than SOC alone group (36.2 vs 51.1%, OR 0.54, 95% CI 0.30–0.97, p = 0.040). The effect on mortality was more pronounced in patients who did not require intubation (10.9 vs 34.0%, OR 0.24, 95% CI 0.09–0.66, p = 0.006) and with early administration (within 72 hours of admission) of ULI (30.7 vs 57.9%, OR 0.32, 95% CI 0.11–0.91, p = 0.032). On multivariate analysis, only intubation predicted mortality (adjusted OR 10.13, 95% CI 3.77–27.25, p<0.0001) and the effect of ULI on survival was not significant (adjusted OR 0.58, 95% CI 0.22–1.52, p = 0.270). Conclusion: Given the limited options for COVID-19 patients treated in ICU, early administration of ULI may be helpful, especially in patients not requiring intubation to improve the outcomes. Further, a large, randomized study is warranted to confirm these findings.

Comparison of cardiac output in OPCAB: bolus thermodilution technique versus pulse contour analysis.

The study was designed to evaluate the clinical agreement between intermittent bolus thermodilution technique and pulse contour analysis technique. Sixty patients with normal left ventricular function undergoing elective off-pump coronary bypass surgery were included in this prospective study. In addition to routine monitoring, a 7.5F pulmonary artery thermodilution catheter via right internal jugular vein and a 4F arterial thermodilution catheter into femoral artery were also placed. Cardiac output measurements were compared before induction, after induction, after sternotomy, during the various anastomoses, post-protamine and post-sternal closure. Statistical analysis was performed using analysis of agreement to assure bias distribution of differences between the two methods by using Bland and Altman analysis. The cardiac output values obtained at preinduction, post-induction, and post-sternal closure time points showed good agreement, whereas the values obtained during the various anastomoses showed significant differences (p <0.05). Therefore it was concluded that pulse contour analysis cannot be relied upon completely whenever there is a change in the position of heart or alteration in systemic vascular resistance. But the trends in cardiac output were in complete agreement during the entire procedure.

Robotically enhanced coronary artery bypass surgery.

BACKGROUND: Robotically enhanced telemanipulation surgery is a fast developing technique which allows totally endoscopic cardiac surgery with utmost precision and perfection on both beating heart as well as arrested heart. METHODS AND RESULTS: Between December 2002 and February 2004, 125 patients underwent robotically enhanced coronary artery bypass surgery using the da Vinci telemanipulation system (Intuitive Surgical Inc., California). Eleven patients underwent totally endoscopic coronary artery bypass surgery. Of them 9 were done on beating heart while 2 were done on arrested heart. One hundred and fourteen patients had endoscopic takedown of internal mammary artery followed by minimally invasive direct coronary artery bypass in 63 patients and left anterolateral thoracotomy in 51 patients. The internal mammary artery mobilization time was 42 min (35-74 min) while the left internal mammary artery to left anterior descending artery anastomosis time ranged from 20 to 36 min for the totally endoscopic coronary artery bypass patients. In 1 patient, the right internal mammary artery was anastomosed to diagonal artery totally endoscopically. The mean internal mammary artery flow by Doppler measurement done in patients undergoing minimally invasive direct coronary artery bypass was 64 ml/min. Seven patients required conversion to median sternotomy and coronary bypass surgery on beating heart. The mean intensive care unit stay was 1.2 days and the mean hospital stay 4.5 days. There was 1 in-hospital mortality. All 11 patients who underwent totally endoscopic bypass surgery had coronary angiography done at 3 months interval which showed 100% patency in 10 patients while one patient had 50% anastomotic narrowing for which coronary angioplasty was done in the same sitting. CONCLUSIONS: Using telematic technology, a complete endoscopic anastomosis is possible in both single vessel and suitable double vessel disease patients. The use of robotics is now extended to achieve complete myocardial revascularization by harvesting both the internal mammary arteries and making a small thoracotomy for direct anastomosis as well.

Mechanical ventilation in the prone position: a strategy for acute respiratory failure after cardiac surgery.

Ventilation in the prone position, initially introduced in respiratory therapy to improve the drainage of secretions, has been used in intensive care to improve oxygenation. We report a case of an obese male patient who underwent elective coronary artery bypass grafting and had low PaO2 in the postoperative period. The PaO2 improved whenever the patient was ventilated in the prone position. On each occasion, oxygenation improved without any change in the hemodynamic parameters. The PaO2 increased from 57.8 to 249.7 mmHg on the first occasion, from 48.7 to 194.6 mmHg on the second and 62.5 to 199.7 mmHg on the third at an FIO2 of 1.0. The shunt fraction (Qva/Qt) decreased from 43.6% to 7.2% on the first occasion and from 46.7% to 12.5% on the second. Ventilation in the prone position can be an effective method for improving oxygenation in patients suffering from postoperative acute respiratory failure who are not responding to other ventilatory strategies.

Changes in transfusion therapy guided by thromboelastograph in cardiac surgery.

This study was conducted to determine the use of thromboelastograph in predicting excessive postoperative bleeding, detecting coagulopathy related bleeding, reducing usage of blood and blood products and aiding reexploration decisions. One hundred fifty patients undergoing coronary artery bypass graft surgery under cardiopulmonary bypass were randomized and studied prospectively in two equal groups. In the study group, celite activated heparinase pretreated blood samples, 30 minutes after protamine administration were subjected to thromboelastographic analysis and blood and blood component therapy was administered based on thromboelastograph values, if they had significant bleeding. In the control group transfusion therapy was based on routine coagulation tests and clinical judgement of the surgeon. Patients who bled 100ml / hour in the first three hours or 300 ml in the first three hours and 75 ml/hour in the next three hours were considered significant bleeders. Haematocrit at 0,6,12,18,24,30 and 36 hours of shifting to intensive care unit were noted. Accuracy of thromboelastograph in predicting excess postoperative bleeding was found to be 92%. Consumption of whole blood, packed red blood cells and fresh frozen plasma (p values 0.03, 0.05, 0.001 respectively) was significantly less in the study group. There was poor correlation between postoperative bleeding and platelet count but those who did not bleed had a significantly higher platelet count as compared to those who did. Except at 30 hours, haematocrit was significantly higher in the study group up to 36 hours. Thromboelastograph is a useful diagnostic tool to detect coagulopathies following cardiopulmonary bypass. It helps in instituting appropriate blood and blood component therapy thereby avoiding unnecessary transfusion and associated risks. Accurate detection of coagulopathy is possible with heparinase pretreatment of the blood sample.

Carotid endarterectomy under regional analgesia:a retrospective study (1988-1999).

The procedure of carotid endarterectomy is more or less standardized. Controversies persist on many technical issues, one of which is general versus regional anaesthesia. We retrospectively evaluated the influence of regional analgesia on perioperative complications, the hospital stay and the perioperative mortality after carotid endarterectomy in 53 patients. All the patients in the study received deep cervical block regional anaesthesia (Winne's technique) for carotid endarterectomy. Indications for surgery included transient ischaemic haemodynamically significant stenosis. Shunt was used in 7 cases (13.2%). General anaesthesia was supplemented in 2 patients (3.8%). There was no perioperative mortality. Permanent non-fatal neurologic deficit occurred in 1 patient (1.9%) and temporary neurologic Deficit occurred in 1 patient (1.9%). The mean ICU stay was 1.85 (+/-0.82) days and the hospital stay was 5.2 (+/-1.14) days. On the basis of our data we believe that under regional anaesthesia carotid endarterectomy can be performed with acceptable complications and that regional anaesthetic technique is safe and well tolerated by the patients.

Efficacy of reiki on patients undergoing coronary artery bypass graft surgery.

Reiki was administered to 50 patients out of 100 patients with normal left ventricular function scheduled for elective coronary artery bypass grafting. Blood components and inflammatory markers were estimated at various time points. Haemodynamic parameters, psychological analysis, intensive care unit stay,incidence of infection, chest tube drainage and mortality were recorded. Haemodynamic parameters and use of blood components were similar in both groups. Interleukin-6 were significantly lower in the preoperative period in the Reiki group, but showed similar trends in both the groups in the post-operative period. The psychological analysis assessed by World Health Organisation quality of life and General Health Questionnaire revealed that social relationships improve once patient is in his own surroundings and with his own people in both the groups. Psychological domain showed significant difference, six day after surgery in the Reiki group. This study concludes that Reiki is a time consuming process with no significant clinical benefit.

Propofol -fentanyl anaesthesia: a comparison with isoflurane-fentanyl anaesthesia in coronary artery bypass graft surgery.

The haemodynamic effects of propofol -fentanyl anaesthesia (n=25) were compared with isoflurane-fentanyl anaesthesia (n=25) in patients with normal left ventricular ejection fraction (>45%) undergoing coronary artery bypass graft surgery under cardiopulmonary bypass. In the propofol group (Group P), anaesthesia was induced with midoazolam 2.5 to 5.0 mg, fentanyl 5mg/kg, pancuronium 0.1 mg/kg and propofol 1-2 mg/kg and was maintained with propofol infusion 10 mg/kg/hr till sternotomy, followed by 3 mg/kg/hr till skin closure. In the inhalational group (Group I) anaesthesia was induced with midazolam, fentanyl, pancuronium in the same doses and sleep dose of thiopentone and was maintained with oxygen : nitrous oxide (50:50) and isoflurane (0.5-1%). Additional fentanyl 2.5 microg/kg was given before sternotomy. Haemodynamic measurements were made before induction, after induction, after sternotomy, after heparinisation, after release of aortic cross clamp, post-bypass, post-sternal closure and on arrival in the recovery room. Post-bypass the cardiac index was higher in Group P (2.90+/- 0.76 v/s 2.40 +/- 0.40, p <0.05). Similarly post-bypass stroke volume index was higher in Group P (379.32 +/- 6.31 v/s 26.78 +/- 6.24, p<0.05). Patients in Group P were extubated earlier as compared to Group I (379.50 +/- 69 min v/s 453.00 +/- 134 min, p<0.05). This study suggests that propofol may be a suitable adjunct to opioid anaesthesia in patients with normal left ventricular ejection fraction undergoing coronary artery bypass graft surgery.

Sevoflurane for induction and intubation in children undergoing congenital cardiac surgery.

The induction and intubation characteristics of sevoflurane were studied prospectively in 23 children, aged 3 months to 6 years (mean 24 +/- 20.25), undergoing repair of congenital cardiac defects. After premedication with syrup chloral hydrate (75mg/kg orally), anaesthesia was induced with 8% sevoflurane and 50% nitrous oxide in oxygen. Nasal endotracheal intubation was performed once the pupils were small and central, without the use of neuromuscular blocking agents or opioids. Characteristics of induction and intubating conditions were recorded. Induction time (from application of face mask to loss of eyelash reflex) was 43.7 +/- 4.57 secs (mean +/- SD). Mean intubation time was 149.1 +/- 15.6 secs. Intubating conditions were excellent in 21 patients (91.3%) and good in 2 patients (80.7%). Haemodynamic parameters (heart rate, rhythm, and systolic blood pressure) were recorded at loss of eyelash reflex, immediately before intubation and at 1, 3 and 5 min after intubation. All children remained haemodynamically stable throughout induction and there were no adverse airway events.

Haemodynamic effects of leg raising in patients undergoing coronary artery bypass grafting.

Twenty patients undergoing elective coronary artery bypass grafting were studied prospectively to evaluate the haemodynamic effects of passive leg raising. The patients were divided into two groups: those having good left ventricular function with ejection fraction of 0.50 or more (group I, n = 10) and those having poor left ventricular function with ejection fraction of upto 0.35 (group II, n = 10). Morphine-based anaesthetic technique was used and standard haemodynamic measurements were obtained at following stages: (1) control--20 to 30 min after induction of anaesthesia; (2) one minute, and (3) five min after raising both the legs; (4) one min, and (5) five min after the legs were repositioned. In group I, heart rate decreased from 71 +/- 9 to 66 +/- 8 beats/min (p < 0.001) at stage 1 and persisted throughout the study period. This was accompanied by a decrease in cardiac index, although, the statistical significance was achieved at stage 3 and 4 only. The haemodynamic changes observed in group II were of more severe magnitude. The heart rate decreased from 90 +/- 13 to 84 +/- 13 beats/min at stage 1 (p < 0.05) and persisted throughout the study with maximum decrease of 14 percent occurring at stage 3. The cardiac index decreased significantly from 2.4 +/- 0.3 to 2.0 +/- 0.5 L/min/m2 (p < 0.05) at stage 1. This persisted throughout the study except that it recovered at stage 4. The maximum decrease in cardiac index (20%) occurred at stage 2. In addition, systemic vascular resistance increased significantly from 1458 +/- 255 to 1830 +/- 420 dyne.sec.cm-5 (p < 0.05) at stage 1 and persisted throughout the study period. We conclude that passive leg raising should be undertaken with caution in patients with coronary artery disease especially in those who have poor left ventricular function.

Minimally invasive atrial septal defects repair.

This study reviews the current method of atrial septal defect closure at our institute with a minimally invasive approach without median sternotomy. From September 1997 to August 1998, 37 patients (13 males, 24 females) with mean age 36.5 years (range 18-67 years) underwent atrial septal defect closure by right anterior thoracotomy. Femoral vessels were cannulated through a small groin incision and extracorporeal circulation was established. Venous drainage was assisted with a centrifugal pump. Aortic crossclamping was performed through the intact chest wall using a special transthoracic clamp with sliding rod design inserted through a separate tiny 3 mm incision in the right second intercostal space in the mid clavicular line. Mean duration of cardiopulmonary bypass and aortic crossclamp time was 35 +/- 14 and 23 +/- 7 minutes respectively; mean endotracheal intubation time after surgery 6.2 +/- 3 hours; mean ICU stay 10.6 +/- 2.8 hours; mean length of thoracotomy incision 7.2 +/- 1.8 cm; and, mean hospital stay 4.2 +/- 1.8 days. There was no post-operative neurological dysfunction or femoral cannulation related complication. There was no perioperative or late mortality. No residual atrial septal defect was observed by transoesophageal echocardiography in any patient. The procedure described here provides secure closure of the atrial septal defects in minimally invasive fashion with good results.

Comparison of intubating conditions and haemodynamic effects of rocuronium with vecuronium in patients with poor left ventricular ejection fraction undergoing coronary artery bypass graft surgery.

To compare the haemodynamic effects and intubating conditions of rocuronium and vecuronium, 20 patients of either sex with poor left ventricular function (ejection fraction <35%) scheduled for coronary artery bypass surgery were randomly divided into two equal groups. All patients were premedicated with lorazepam and morphine and induced with morphine, midazolam, thiopentone and either vecuronium (0.1 mg/kg) or rocuronium (0.6 mg/kg) as muscle relaxant. All patients were intubated after 3 minutes in the vecuronium group and 90 seconds in the rocuronium group by the same anaesthesiologist. Monitoring in all cases included neuromuscular (train of four- TOF), systemic and pulmonary arterial pressures, cardiac output and calculated haemodynamic variables. Demographic (age, sex and mean ejection fraction) and haemodynamic variables were comparable in both the groups. A significant suppression of the TOF in the vecuronium group was observed despite better intubating conditions in the rocuronium group. The heart rate at 3 minutes and mean arterial pressure at 1 minute was higher in the vecuronium group as compared to the rocuronium group. There were no other significant haemodynamic differences in both the groups. We conclude that rocuronium does provide better intubating conditions at 90 seconds than vecuronium at 3 minutes with no significant differences in the haemodynamic parameters between the two; however, the train of four response does not correlate with intubating conditions.

Role of Preoperative Upper Gastrointestinal Endoscopy in Preventing postoperative Upper Gastrointestinal Bleed in Patients Undergoing CABG.

One hundred and three patients (Group A), mean age 55.81 +/- 8.54 years, 94 males and 9 females, scheduled for coronary artery bypass graft (CABG) surgery were subjected to preoperative upper gastro-intestinal (UGI) endoscopy. 51.5% of these were found to have significant mucosal lesions in the UGI tract. Twenty one (20.4%) had severe lesions which could have bled, warranting postponement of their surgery. All of these 21 were treated with Omeprezole 20 mg / day for a mean of 35.87 +/- 4.64 days and subjected to check endoscopy after the treatment. 16 of these 21 patients were taken up for CABG after the lesions had healed. Five deferred surgery. None of the 103 patients had a postoperative UGI bleed. A retrospective analysis of 1274 patients (group B) was carried out for number of patients (42) having postoperative UGI bleed. The results of group A and group B were then compared. Patients in group A had significant lower incidence of postoperative UGI bleed than those in group B. Postoperative hospital stay in patients of UGI bleed in group B was 24.71 +/- 20.88 (range 8 days - 129 days). In group A it was 14.34 +/- 12.44 days (range 7 days - 88 days). The difference is statistically highly significant. It appears that patients who have postoperative UGI bleed probably bleed from pre existing lesions. We conclude that preoperative UGI endoscopy is a valuable tool in preventing postoperative UGI bleed.

Clinical evaluation of the leukogard-6 arterial line filter.

To assess the leucocyte depleting characteristics of the Pall leukogard-6 arterial line leucocyte depleting filter, it was incorporated in the extracorporeal circuit of 30 patients with normal left ventricular function scheduled for elective coronary artery bypass grafting. The Intersept Medtronic 40 micro arterial line filter which is normally used at our centre was used in 29 similar patients. Blood samples were drawn for estimation of total and differential leucocyte and platelet counts, blood gas analysis, superoxide dismutase levels and renal function tests at various time points. Ventilation time, length of ICU stay and incidence of infection were recorded. No significant difference was observed between the two groups regarding total leucocyte count, percentage of neutrophils and lymphocytes, platelet count, arterial oxygen and carbon dioxide tensions, pulmonary vascular resistance, ventilation time and postoperative infection. A significant difference was observed between the prebypass levels of superoxide dismutase 89.63 +/- 49.69 SOD units/ml, and 24 hours post bypass levels 66.62 +/- 36.23 SOD units/ml, (p<0.01), in the control group. In the leukogard filter group, the difference between pre bypass levels of superoxide dismutase 82.47 +/- 50.58 SOD units/ml and 24 hours post bypass 73.44 +/- 41.10 SOD units/ml, (p>0.05), was not significant. This indicated less free radical activity in the leukogard filter group, but this beneficial effect of the leukogard-6 filter did not correlate with any clinical parameter. In this study, the leukoard-6 filter did not exhibit leucocyte depleting characteristics following cardiopulmonary bypass and is unlikely to be of significant advantage when incorporated in the extracorporeal circuit for coronary artery bypass grafting, in patients with normal ejection fraction.