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

Alexandre Lima, Michel E van Genderen, Jasper van Bommel, Eva Klijn, Tim Jansem, Jan Bakker, Alexandre Lima, Michel E van Genderen, Jasper van Bommel, Eva Klijn, Tim Jansem, Jan Bakker

Abstract

Introduction: Recent clinical studies have shown a relationship between abnormalities in peripheral perfusion and unfavorable outcome in patients with circulatory shock. Nitroglycerin is effective in restoring alterations in microcirculatory blood flow. The aim of this study was to investigate whether nitroglycerin could correct the parameters of abnormal peripheral circulation in resuscitated circulatory shock patients.

Methods: This interventional study recruited patients who had circulatory shock and who persisted with abnormal peripheral perfusion despite normalization of global hemodynamic parameters. Nitroglycerin started at 2 mg/hour and doubled stepwise (4, 8, and 16 mg/hour) each 15 minutes until an improvement in peripheral perfusion was observed. Peripheral circulation parameters included capillary refill time (CRT), skin-temperature gradient (Tskin-diff), perfusion index (PI), and tissue oxygen saturation (StO2) during a reactive hyperemia test (RincStO2). Measurements were performed before, at the maximum dose, and after cessation of nitroglycerin infusion. Data were analyzed by using linear model for repeated measurements and are presented as mean (standard error).

Results: Of the 15 patients included, four patients (27%) responded with an initial nitroglycerin dose of 2 mg/hour. In all patients, nitroglycerin infusion resulted in significant changes in CRT, Tskin-diff, and PI toward normal at the maximum dose of nitroglycerin: from 9.4 (0.6) seconds to 4.8 (0.3) seconds (P < 0.05), from 3.3 °C (0.7 °C) to 0.7 °C (0.6 °C) (P < 0.05), and from [log] -0.5% (0.2%) to 0.7% (0.1%) (P < 0.05), respectively. Similar changes in StO2 and RincStO2 were observed: from 75% (3.4%) to 84% (2.7%) (P < 0.05) and 1.9%/second (0.08%/second) to 2.8%/second (0.05%/second) (P < 0.05), respectively. The magnitude of changes in StO2 was more pronounced for StO2 of less than 75%: 11% versus 4%, respectively (P < 0.05).

Conclusions: Dose-dependent infusion of nitroglycerin reverted abnormal peripheral perfusion and poor tissue oxygenation in patients following circulatory shock resuscitation. 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.

Figures

Figure 1
Figure 1
Flowchart of the study protocol. Time points of the study were defined as baseline 1 before nitroglycerin infusion (TBL1), time point when peripheral perfusion was normalized at the maximum dose of nitroglycerin (TMX), and baseline 2 recorded 30 minutes after cessation of nitroglycerin infusion (TBL2). NTG, nitroglycerin.
Figure 2
Figure 2
Temporal behavior of peripheral circulation parameters (CRT, Tskin-diff, and PI) and StO2-derived variables (StO2, RincStO2, and RdecStO2) during study protocol. Time points are defined as before nitroglycerin infusion (TBL1), at the maximum dose of nitroglycerin (TMX), and 30 minutes after cessation of nitroglycerin (TBL2). CRT, capillary refill time (seconds); PIlog, log of perfusion index (percentage); RdecStO2, rate of peripheral tissue oxygenation desaturation during arterial occlusion (percentage per minute); RincStO2, rate of peripheral tissue oxygenation recovery after arterial occlusion (percentage per second); StO2, peripheral tissue oxygenation (percentage); Tskin-diff, forearm-to-fingertip skin-temperature gradient (degrees Celsius). Lines represent individual values for each patient. Bars are mean ± 95% confidence interval (CI).

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