A Multicentric, Randomized, Controlled Phase III Study of Centhaquine (Lyfaquin®) as a Resuscitative Agent in Hypovolemic Shock Patients.

INTRODUCTION: Centhaquine (Lyfaquin®) showed significant safety and efficacy in preclinical and clinical phase I and II studies. METHODS: A prospective, multicentric, randomized phase III study was conducted in patients with hypovolemic shock, systolic blood pressure (SBP) ≤ 90 mmHg, and blood lactate levels ≥ 2 mmol/L. Patients were randomized in a 2:1 ratio to the centhaquine group (n = 71) or the control (saline) group (n = 34). Every patient received standard of care (SOC) and was followed for 28 days. The study drug (normal saline or centhaquine 0.01 mg/kg) was administered in 100 mL of normal saline infusion over 1 h. The primary objectives were to determine changes (mean through 48 h) in SBP, diastolic blood pressure (DBP), blood lactate levels, and base deficit. The secondary objectives included the amount of fluids, blood products, and vasopressors administered in the first 48 h, duration of hospital stay, time in intensive care units, time on ventilator support, change in acute respiratory distress syndrome (ARDS), multiple organ dysfunction syndrome (MODS), and the proportion of patients with 28-day all-cause mortality. RESULTS: The demographics of patients and baseline vitals in both groups were comparable. The cause of hypovolemic shock was trauma in 29.4 and 47.1% of control group and centhaquine group patients, respectively, and gastroenteritis in 44.1 and 29.4%, respectively. Shock index (SI) and quick sequential organ failure assessment at baseline were similar in the two groups. An equal amount of fluids and blood products were administered in both groups during the first 48 h of resuscitation. A lesser amount of vasopressors was needed in the first 48 h of resuscitation in the centhaquine group. An increase in SBP from baseline was consistently higher up to 48 h (12.9% increase in area under the curve from 0 to 48 h [AUC0-48]) in the centhaquine group than in the control group. A significant increase in pulse pressure (48.1% increase in AUC0-48) in the centhaquine group compared with the control group suggests improved stroke volume due to centhaquine. The SI was significantly lower in the centhaquine group from 1 h (p = 0.032) to 4 h (p = 0.049) of resuscitation. Resuscitation with centhaquine resulted in a significantly greater number of patients with improved blood lactate (control 46.9%; centhaquine 69.3%; p = 0.03) and the base deficit (control 43.7%; centhaquine 69.8%; p = 0.01) than in the control group. ARDS and MODS improved with centhaquine, and an 8.8% absolute reduction in 28-day all-cause mortality was observed in the centhaquine group. CONCLUSION: Centhaquine is an efficacious resuscitative agent for treating hypovolemic shock. The efficacy of centhaquine in distributive shock is being explored. TRIAL REGISTRATION: Clinical Trials Registry, India; ctri.icmr.org.in, CTRI/2019/01/017196; clinicaltrials.gov, NCT04045327.

A multicentric, randomized, controlled phase III study of centhaquine (Lyfaquin ® ) as a resuscitative agent in hypovolemic shock patients.

INTRODUCTION: Centhaquine (Lyfaquin ® ) showed significant safety and efficacy in preclinical and clinical phase I and II studies. METHODS: A prospective, multicentric, randomized phase III study was conducted in patients with hypovolemic shock having systolic blood pressure (SBP) of ≤90 mm Hg and blood lactate levels of ≥2 mmol/L. Patients were randomized in a 2:1 ratio, 71 patients to the centhaquine group and 34 patients to the control (saline) group. Every patient received standard of care (SOC) and was followed for 28 days. The study drug (normal saline or centhaquine (0.01 mg/kg)) was administered in 100 mL of normal saline infusion over 1 hour. The primary objectives were to determine changes (mean through 48 hours) in SBP, diastolic blood pressure (DBP), blood lactate levels, and base deficit. The secondary objectives included the amount of fluids, blood products, vasopressors administered in the first 48 hours, duration of hospital stay, time in ICU, time on the ventilator support, change in patient's Acute Respiratory Distress Syndrome (ARDS), Multiple Organ Dysfunction Syndrome (MODS) scores, and the proportion of patients with 28-day all-cause mortality. RESULTS: The demographics of patients and baseline vitals in both groups were comparable. Trauma was the cause of hypovolemic shock in 29.41% of control and 47.06% of centhaquine, gastroenteritis in 44.12% of control, and 29.41% of centhaquine patients. An equal amount of fluids and blood products were administered in both groups during the first 48 hours of resuscitation. A lesser amount of vasopressors was needed in the first 48 hours of resuscitation in the centhaquine group. An increase in SBP from the baseline was consistently higher in the centhaquine group than in the control. A significant increase in pulse pressure in the centhaquine group than the control group suggests improved stroke volume due to centhaquine. The shock index was significantly lower in the centhaquine group than control from 1 hour (p=0.0320) till 4 hours (p=0.0494) of resuscitation. Resuscitation with centhaquine had a significantly greater number of patients with improved blood lactate and the base deficit than the control group. ARDS and MODS improved with centhaquine, and an 8.8% absolute reduction in 28-day all-cause mortality was observed in the centhaquine group. CONCLUSION: Centhaquine is a highly efficacious resuscitative agent for treating hypovolemic shock. The efficacy of centhaquine in distributive shock due to sepsis and COVID-19 is being explored. TRIAL REGISTRATION: Clinical Trials Registry, India; ctri.icmr.org.in, CTRI/2019/01/017196; clinicaltrials.gov, NCT04045327 . KEY SUMMARY POINTS: A multicentric, randomized, controlled trial was conducted to evaluate the efficacy of centhaquine in hypovolemic shock patients.One hundred and five patients were randomized 2:1 to receive centhaquine or saline. Centhaquine was administered at a dose of 0.01 mg/kg in 100 mL saline and infused over 1 hour. The control group received 100 mL of saline over a 1-hour infusion.Centhaquine improved blood pressure, shock index, reduced blood lactate levels, and improved base deficit. Acute Respiratory Distress Syndrome (ARDS) and Multiple Organ Dysfunction Syndrome (MODS) score improved with centhaquine.An 8.8% absolute reduction in 28-day all-cause mortality was observed in the centhaquine group. There were no drug-related adverse events in the study.

Laparoscopic Versus Open Sigmoid Loop Colostomy: A Comparative Study from a Cohort of 62 Patients Requiring Temporary Faecal Diversion at a Tertiary Care Center in North India.

BACKGROUND: Over decades, colostomies have been done through open method, but laparoscopic creation of an intestinal stoma is safe, feasible and has distinct advantages over conventional techniques in specific procedures. The aim of this study compares operative and short-term outcomes of laparoscopic and open sigmoid loop colostomy formation for temporary fecal diversion. SUBJECTS AND METHODS: A single institution, comparative study conducted in the department of surgery for patients who underwent either laparoscopic or open sigmoid loop colostomy. The 2 years' study was from December 1, 2013, to November 30, 2015. Subjects were prospectively enrolled in the study after informed consent, both genders of >12 years of age. Data analysis was done using Statistical Package for Social Sciences version 21.0. Variables were tested by Kolmogorov-Smirnov test, compared using unpaired t-test/Mann-Whitney Test, Chi-square test/Fisher's exact test. P < 0.05 was considered statistically significant. RESULTS: Sixty-two patients were enrolled; laparoscopy group - 29 patients (46.77%) versus open group - 33 patients (53.22%). Laparoscopic group/open surgery group showed less blood loss (20.69 + 17.71 ml / 121.97 + 35.29ml, P-value 0.0005), lower requirement of analgesics (4.28 ± 1.76 days/6.88 ± 2.75 days), shorter hospital stay (8.79 ± 5.57 days and 11.73 ± 6.61 days, P = 0.001), early return of the bowel function and tolerance to diet. Complications and readmission requirement for any complication was lower in the laparoscopic group. CONCLUSIONS: Laparoscopic sigmoid loop colostomy is a simple alternative to open sigmoid loop colostomy with respect to postoperative pain, earlier return of bowel function, lower analgesic requirement, and lesser hospital stay.

Kasabach-Merritt Syndrome Associated With a Large Cavernous Splenic Hemangioma Treated With Splenectomy: A Surgeon's Introspection of an Uncommon, Little Read, and Yet Complex Problem-Review Article.

Cavernous hemangiomas of the spleen are small benign lesions found incidentally, majority of times while patients are being investigated for some other disease and patients remain asymptomatic otherwise for this condition. The natural history of cavernous hemangiomas of spleen is slow, symptoms or complications, when present, occur late, they are rarely large and can manifest as a palpable non-tender mass in the left upper quadrant. A very rare syndrome is associated with this condition called Kasabach-Merritt syndrome (KMS), which is defined as diffuse cavernous hemangioma of the spleen alongwith anemia, thrombocytopenia, and coagulopathy. Perioperative diagnosis can be confirmed by imaging study which can be CT, MRI, or ultrasound. Splenectomy is considered the treatment of choice for such patients with symptoms. To our knowledge, a very few cases have been reported so far. The purpose of writing this review article is the reporting of this rare case and to provide some experience related to the management of this condition in a patient with KMS.

Thoracic duct injury following esophagectomy in carcinoma of the esophagus: ligation by the abdominal approach.

BACKGROUND: Thoracic duct injury (TDI) is a potentially lethal complication of esophagectomy. There is no consensus regarding when and how to intervene in these injuries. Both thoracic and abdominal approaches have been used. METHODS: Esophagectomies performed for cancer of the esophagus (n = 104) from October 2003 to July 2011 were analyzed for TDI. Diagnosis, histological type, stage, and location of tumor, neoadjuvant therapy, trans-thoracic or trans-hiatal procedure performed, nature and amount of drain output, and levels of triglyceride in the effluent were analyzed. Management of these injuries and morbidity and mortality associated with the approach taken were reviewed. RESULTS: We observed chylothorax in 9 patients. All nine patients had undergone trans-hiatal esophagectomy. All patients eventually required surgical intervention. Mass ligation of the thoracic duct was performed via the thoracic route in three patients and via the trans-abdominal approach in six others. Thoracic duct ligation was successful in all patients. One patient required a second laparotomy and repeat ligation of the duct. There were two postoperative deaths; both these patients had ligation by the thoracic route. CONCLUSIONS: Trans-abdominal ligation of the thoracic duct in patients with chylothorax after esophagectomy is technically easy and safe. It may be preferred over the trans-thoracic approach, especially after an initial trans-hiatal esophagectomy.