Short-term effects of terlipressin bolus infusion on sublingual microcirculatory blood flow during septic shock

Morelli, Andrea; Donati, Abele; Ertmer, Christian; Rehberg, Sebastian; Orecchioni, Alessandra; Russo, Alessandro; Pelaia, P; Pietropaoli, P; Westphal, Martin

doi:10.1007/s00134-011-2148-x

Cited by 28 publications

(13 citation statements)

References 21 publications

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“…In harmony with the effects on the microcirculation, and in line with previous experimental and clinical studies [ 17 - 19 , 23 ], we did not notice differences in arterial pH or in lactate concentrations following TP or AVP administration, suggesting a lack of drug-related impairment of cellular oxygenation as well as the absence of differences in resuscitation quality between groups. In this context, it is also important to note that the multicenter VASST study [ 16 ] demonstrated no differences between AVP and sole NE in the rate of overall adverse events.…”

Section: Discussionsupporting

confidence: 92%

Effects of vasopressinergic receptor agonists on sublingual microcirculation in norepinephrine-dependent septic shock

et al. 2011

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IntroductionThe present study was designed to determine the effects of continuously infused norepinephrine (NE) plus (1) terlipressin (TP) or (2) arginine vasopressin (AVP) or (3) placebo on sublingual microcirculation in septic shock patients. The primary study end point was a difference of ≥ 20% in the microvascular flow index of small vessels among groups.MethodsThe design of the study was a prospective, randomized, double-blind clinical trial. NE was titrated to maintain mean arterial pressure (MAP) between 65 and 75 mmHg after establishment of normovolemia in 60 septic shock patients. Thereafter patients (n = 20 per group) were randomized to receive continuous infusions of either TP (1 μg/kg/hour), AVP (0.04 U/minute) or placebo (isotonic saline). In all groups, open-label NE was adjusted to maintain MAP within threshold values if needed. The sublingual microcirculatory blood flow of small vessels was assessed by sidestream dark-field imaging. All measurements, including data from right heart catheterization and norepinephrine requirements, were obtained at baseline and 6 hours after randomization.ResultsTP and AVP decreased NE requirements at the end of the 6-hour study period. The data are medians (25th and 75th interquartile ranges (IQRs)): 0.57 μg/kg/minute (0.29 to 1.04) vs. 0.16 μg/kg/minute (0.03 to 0.37) for TP and 0.40 μg/kg/minute (0.20 to 1.05) vs. 0.23 μg/kg/minute (0.03 to 0.77) for AVP, with statistical significance of P < 0.05 vs. baseline and vs. placebo. There were no differences in sublingual microcirculatory variables, systemic hemodynamics, oxygen transport and acid-base homeostasis among the three study groups during the entire observation period. The proportions of perfused vessels increased in relation to baseline within all study groups, and there were no significant differences between groups. The specific data were as follows (median (IQR)): 9.7% (2.6 to 19.8) for TP, 8.9% (0.0 to 17.8) for AVP, and 6.9% (3.5 to 10.1) for placebo (P < 0.05 vs. baseline for each comparison), as well as perfused vessel density 18.6% (8.6 to 36.9) for TP, 20.2% (-3.0 to 37.2) for AVP, and 11.4% (-3.0 to 19.4) for placebo (P < 0.05 vs. baseline for each comparison).ConclusionsThe present study suggests that to achieve a MAP of 65 to 75 mmHg in septic patients treated with NE, the addition of continuously infused low-dose TP or AVP does not affect sublingual microcirculatory blood flow. In addition, our results suggest that microcirculatory flow abnormalities are mainly related to other factors (for example, volume status, timing, hemodynamics and progression of the disease) rather than to the vasopressor per se.Trial registrationClinicalTrial.gov NCT00995839

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Section: Discussionsupporting

confidence: 92%

Effects of vasopressinergic receptor agonists on sublingual microcirculation in norepinephrine-dependent septic shock

et al. 2011

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“…Persistent microvascular alterations were associated with organ failure and worse outcome . The microvascular effects of several therapies have been evaluated . Sidestream dark field technology was recently found to have other potential applications, such as in plastic surgery, dermatology and oncology …”

Section: Resultsmentioning

confidence: 99%

“…14,16 The microvascular effects of several therapies have been evaluated. [17][18][19][20][21][22] Sidestream dark field technology was recently found to have other potential applications, such as in plastic surgery, 23 dermatology 24 and oncology. 25 Several microvascular beds (intestine, 26 liver, 27 skeletal muscle, 28 brain 29 ) have been explored in disparate animal models.…”

Section: Resultsmentioning

confidence: 99%

Sidestream dark field videomicroscopy for in vivo evaluation of vascularization and perfusion of mammary tumours in HER2/neu transgenic mice

Pierpaoli

Orlando

Donati

et al. 2015

Clin Exp Pharma Physio

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Angiogenesis plays a key role in tumour growth and the formation of metastases. Angiogenesis inhibitors and antivascular agents may prove useful in the treatment of breast cancer. A comprehensive characterization of the vasculature and perfusion of mammary tumours is a prerequisite for developing new specific drugs. We used sidestream dark field videomicroscopy to evaluate in vivo the vascular network of spontaneous mammary tumours in HER2/neu transgenic mice. The tumour masses showed higher vessel density compared with the healthy mammary gland (median (interquartile range) total vessel density 16.8 (13.4-20.5) vs 9.1 (8.1-10.9) mm/mm(2), respectively; P < 0.001). Tumor vessel density was reduced in mice treated with the anti-angiogenesis agent berberine, 12.1 (10.6-13.1) mm/mm(2). Sidestream dark field imaging is a versatile technique that may be useful for understanding the role of angiogenesis in the progression of breast cancer and its relationship with outcome. It may represent a valuable tool for dynamic monitoring of the effects of new anti-angiogenesis therapies.

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“…Il est à noter que les mesures et l'administration des vasoconstricteurs étaient débutées en médiane 36 heures (entre 21 et 52 heures) après le début du choc septique, sachant qu'il existe peut-être un bénéfice à une administration plus précoce, notamment dans les 24 premières heures, où les altérations microcirculatoires sont les plus sévères. Cette hypothèse est supportée par une autre étude de la même année, de la même équipe, qui montrait que l'injection de terlipressine 0,5 mg en bolus, 28 heures après le début du choc septique avec dépendance à la noradrénaline, améliore la microcirculation (MFI, proportion de capillaires perfusés, index d'hétérogénéité) à h6 de l'injection [61]. En revanche, la méthodologie de cette dernière étude était beaucoup moins pertinente (étude interventionnelle, en ouvert, moins de patients).…”

Section: Effets De La Vasopressine Sur La Microcirculation Chez L'animalunclassified

Effets des vasoconstricteurs sur la microcirculation

et al. 2015

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Les théories physiologiques et les modèles animaux nous prédisent souvent un effet néfaste de l'obtention d'une vasoconstriction importante sur la microcirculation. La diminution de la pression capillaire (avec au maximum une fermeture des capillaires en cas de pression extramurale trop forte), de l'hématocrite microcirculatoire, possiblement du débit, et de la densité capillaire possible en sont autant de raisons. En fait, les effets des vasoconstricteurs à disposition sont impossibles à prévoir : la noradrénaline par exemple provoque un effet alphapositif entraînant une augmentation des résistances artériolaires, mais aussi veineuses, avec un effet possible d'augmentation du débit cardiaque par effet précharge et/ou par bêtastimulation. Les effets sur la perfusion intestinale, rénale et microcirculatoire (le plus souvent sublinguale) sont souvent neutres, voire positifs pour la noradrénaline et la terlipressine au décours du choc septique, pour peu qu'une hypovolémie importante ait été traitée auparavant et que les objectifs de pression artérielle moyenne ne dépassent pas 75 mmHg. La phényléphrine semble être difficile d'utilisation et dangereuse pour la microcirculation. La vasopressine requiert probablement des études complémentaires concernant la microcirculation. Enfin, la titration et la décrémentation en cas de signe de dysoxie tissulaire (marbrures cutanées, augmentation du lactate) semblent être de bon sens. Mots clés Microcirculation · Vasoconstricteurs · Sepsis · Noradrénaline · Terlipressine · Adrénaline · Vasopressine · PhényléphrineAbstract Physiology and animal models often predict microvascular negative effects of excessive vasoconstriction. The following are among them: a drop in capillary pressure (even closure of capillaries), a drop in microvascular haematocrit, a possible drop in flow, a possible decrease in capillary density. In fact, the impact of usual vasoconstrictors is difficult to predict, e.g. norepinephrine is an alpha agonist, which simultaneously increases arteriolar but also venular resistances together with a possible increase in cardiac output by beta stimulation or thanks to preload effect. Concerning norepinephrine and probably terlipressin, the effects on splanchnic, renal and most often sublingual microcirculation are globally either positive or neutral if a deep hypovolemia is treated before perfusion of the drug and if mean arterial pressure goal is below 75 mmHg. Phenylephrine seems deleterious and difficult to use. Vasopressin requires more studies concerning microcirculation. Careful titration and even decrementation of the drugs in case of tissue dysoxia (mottling of the skin, the increase of lactate levels) seems to be common sense.

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Short-term effects of terlipressin bolus infusion on sublingual microcirculatory blood flow during septic shock

Cited by 28 publications

References 21 publications

Effects of vasopressinergic receptor agonists on sublingual microcirculation in norepinephrine-dependent septic shock

Effects of vasopressinergic receptor agonists on sublingual microcirculation in norepinephrine-dependent septic shock

Sidestream dark field videomicroscopy for in vivo evaluation of vascularization and perfusion of mammary tumours in HER2/neu transgenic mice

Effets des vasoconstricteurs sur la microcirculation

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