Centhaquine in Shock Management
Centhaquine (Lyfaquin®) is a novel resuscitative agent that targets the vascular bottleneck in hypovolemic shock by activating α2B-adrenergic receptors on venous circulation, improving cardiac output and tissue perfusion while requiring fewer vasopressors compared to standard treatment. 1, 2
Mechanism of Action
- Centhaquine acts specifically on α2B-adrenergic receptors in the venous circulation and central α2A receptors, producing venous constriction that increases venous return to the heart 1
- This mechanism leads to increased cardiac output and reduced systemic vascular resistance, with a net improvement in blood pressure and tissue perfusion 1
- Unlike traditional vasopressors that primarily cause arterial vasoconstriction, centhaquine addresses the "vascular bottleneck" by optimizing venous return 3
Clinical Evidence
- A multicentric, randomized, controlled phase III study demonstrated that centhaquine at 0.01 mg/kg significantly improved resuscitation outcomes in hypovolemic shock patients 2
- Patients receiving centhaquine showed:
- Better systolic blood pressure response compared to control group 2
- Significant improvement in pulse pressure, suggesting improved stroke volume 2
- Lower shock index from 1 hour (p=0.0320) to 4 hours (p=0.0494) of resuscitation 2
- Greater reduction in blood lactate levels, indicating improved tissue perfusion 2
- Reduced need for vasopressors during the first 48 hours of resuscitation 2
- 8.8% absolute reduction in 28-day all-cause mortality 2
Organ Protection Benefits
- Centhaquine has demonstrated renal protective effects in hemorrhagic shock models by:
- Significantly improving renal blood flow compared to vehicle control (p<0.003) 4
- Reducing blood lactate levels (p=0.0064) at 120 minutes post-resuscitation 4
- Showing less histopathological damage to renal tissue 4
- Augmenting hypoxia response through increased HIF-1α expression (p=0.0152) 4
- Decreasing markers of tissue damage and apoptosis 4
Current Position in Shock Management
- Traditional first-line vasopressors for shock management remain norepinephrine for most clinical conditions, with vasopressin and possibly angiotensin II as adjuncts due to their norepinephrine-sparing effects 5
- Centhaquine represents a novel approach that addresses the "vascular bottleneck" in shock, particularly in hypovolemic shock where optimizing venous return is crucial 3, 6
- While conventional management focuses on fluid resuscitation and vasopressors targeting arterial pressure (MAP ≥65 mmHg), centhaquine's mechanism addresses both cardiac output and tissue perfusion 5, 2
Clinical Application
- Centhaquine is administered at a dose of 0.01 mg/kg in 100 mL saline infused over 1 hour 2
- It has shown particular efficacy in hypovolemic shock due to trauma and gastroenteritis 2
- Research is ongoing to explore its efficacy in distributive shock due to sepsis and COVID-19 2
- No drug-related adverse events were reported in clinical trials 2
Precautions and Monitoring
- As with all vasoactive agents, close monitoring of hemodynamic parameters is essential 5
- Monitoring should include blood pressure, heart rate, shock index, lactate clearance, and organ perfusion markers 2
- Overdosage symptoms may include headache, drowsiness, visual disturbances, and cardiovascular collapse, requiring prompt symptomatic treatment 7
Future Directions
- Centhaquine has been approved for marketing in India as Lyfaquin® for hypovolemic/hemorrhagic shock 1
- The US FDA has approved a phase III IND application, with trials anticipated to begin in 2023 1
- Further research is exploring its potential in preventing and treating acute kidney injury associated with hemorrhagic shock 4