nitroglycerin, peripheral perfusion, oxygen saturation

1. Nitroglycerin reverts clinical manifestations of poor peripheral perfusion in patients with circulatory shock

말초관류이상(abnormalities in peripheral perfusion) & 순환기쇼크환자(circulatory shock) ⇒ unfavorable outcome

nitroglycerin ⇒ microcirculatory blood flow ↑

- 목적 : whether nitroglycerin could correct the parameters of abnormal peripheral circulation in resuscitated circulatory shock patients.

Method

- inclusion : circulatory shock and who persisted with abnormal peripheral perfusion despite normalization of global hemodynamic parameters

- 2 mg/hour 시작 → 매 15분 마다 말초 관류가 개선될 때 까지 2배 증량(ex. 4,8.16 mg/hr)

- peripheral circulation parameters : capillary refill time (CRT), skin-temperature gradient (Tskin-diff), perfusion index (PI), and tissue oxygen saturation (StO2) during a reactive hyperemia test (RincStO2)

Result

- 15명 중 4명의 환자가 초기 투여량에 반응함

- 모든 환자에서 maximum dose에서 CRT, Tskin-diff, PI, StO2와 RincStO2는 정상화 경향을 보임

CRT,	Tskin-diff	PI
9.4 (0.6) seconds to 4.8 (0.3) seconds (P <0.05)	3.3°C (0.7°C) to 0.7°C (0.6°C) (P <0.05)	[log] -0.5% (0.2%) to 0.7% (0.1%) (P <0.05)

StO2	RincStO2
75% (3.4%) to 84% (2.7%) (P <0.05)	1.9%/second (0.08%/second) to 2.8%/second (0.05%/second) (P <0.05)

- The magnitude of changes in StO2 was more pronounced for StO2 of less than 75%: 11% versus 4%, respectively (P <0.05).

Conclusion

• 순환 쇼크 후 소생술 받은 환자에서 용량 의존적으로 니트로글리세린이 말초 관류 및 조직 산소화 불량을 복원시킨다.
• Individual requirements of nitroglycerin dose to improve peripheral circulation vary between patients.
• A simple and fast physical examination of peripheral circulation at the bedside can be used to titrate nitroglycerin infusion.

2. Effects of nitroglycerin versus labetalol on peripheral perfusion during deliberate hypotension for sinus endoscopic surgery

Deliberate hypotension is used to provide a bloodless field during functional endoscopic sinus surgery; however, the impact of controlled hypotension during anesthesia on peripheral tissue perfusion has not been extensively evaluated. The aim of this study was to compare the impact of nitroglycerin- versus labetalol induced hypotension on peripheral perfusion.

Nitroglycerin and labetalol are commonly used drugs for controlled hypotension during anesthesia. Both drugs are also used for acute management of emergent hypertension in emergency departments. Nitroglycerin is a direct vasodilator and its main action is through venodilation. Labetalol combines an α1 blocking effect and beta-adrenergic blocking activity to reduce systemic vascular resistance, with little effect on cardiac output. Both drugs were previously compared during controlled hypotension with regard to surgical field quality and blood loss. To date, however, no study has compared the effects of both drugs on peripheral perfusion.

Method

Nitroglycerin	Nitronal® glyceryl trinitrate, 1 mg/mL	diluted by adding 3 mL (3 mg) to 47 mL of 0.9% saline in a 50 mL syringe
Labetalol	Labetalol Hydrochloride Injection®, 5 mg/mL	diluted by adding 10 mL (50 mg) to 40 mL of 0.9% saline in a 50 mL syringe

성분명	초기 용량	titrated rate
nitroglycerin	0.5 μg/kg/min	0.5–2 μg/kg/min
labetalol	0.5 mg/kg/h	0.5–2 mg/kg/h

Result

Conclusion

Results of our study revealed that nitroglycerin-induced deliberate hypotension was associated with more preserved PPI compared with labetalol-induced deliberate hypotension. Both study drugs provided acceptable surgical conditions; however, nitroglycerin infusion appeared to be safer in terms of peripheral tissue perfusion. We also found that using nitroglycerin for induction of controlled hypotension did not impair peripheral tissue perfusion.

nitrolgycerin이 labetalol에 비해 peripheral perfusion에 더 이점이 있을 수 밖에 없는 이유

• NTG는 vasodilator drug임 👉 precapillary inflow pressure 증가로 인해 microcirculatory blood flow가 호전됨
• 반면 labetalol의 경우, α1:β = 1:7로 antagonist effect를 가짐 👉 systemic vascular resistance를 감소시키기는 하지만 NTG보다 그 효과가 적을 것으로 예상

The “art” of hypotensive anesthesia is to achieve proper surgical conditions without suppressing perfusion of vital organs. The risk for impairment of tissue perfusion has been the primary concern that limits the use of deliberate hypotension. However, in our patients, we found that PPI did not decrease in the nitroglycerin group throughout the operation, despite the low blood pressure. Furthermore, serum lactate concentration was not significantly elevated in both groups. Therefore, we believe that deliberate hypotension should not be considered a state of circulatory shock. We assume that, under well-monitored peripheral perfusion, nitroglycerin could be a good choice to induce controlled hypotension if it is surgically indicated.

🌵 NTG 혹은 labetalol의 deliberate hypotension 유발로 인해 관류 손상 위험을 유발한다는 가설로 인해 사용을 제한해야한다는 주장이 있었다. 그러나 환자의 저혈압 상태에도 불구하고 수술 내내 NTG군에서 PPI가 감소되지 않았다. 뿐만 아니라 두 그룹 모두에서 serum lactate의 농도가 유의하게 상승하지 않았다. 따라서 deliberate hypotension이 circulatory shock으로 간주되어서는 안 된다고 생각된다.

결론적으로 말초 관류에 대해 잘 모니터링되는 상태에서 외과적 수술에서 NTG의 사용은 좋은 선택지가 될 것이다.

reference:

1) Lima, Alexandre, et al. "Nitroglycerin reverts clinical manifestations of poor peripheral perfusion in patients with circulatory shock." Critical Care 18.3 (2014): 1-8.

2) Zayed, Marwa, et al. "Effects of nitroglycerin versus labetalol on peripheral perfusion during deliberate hypotension for sinus endoscopic surgery: a randomized, controlled, double-blinded trial." BMC anesthesiology 20.1 (2020): 1-9.

3) 약학정보원