Continuous low-dose infusion of terlipressin as a rescue therapy in meningococcal septic shock
Case Report
Continuous low-dose infusion of terlipressin as a Rescue therapy in meningococcal septic shock
We report the case of a 3-year-old girl who was transferred to our institution with septic shock and extensive purpura. Despite aggressive fluid resuscitation and cate-
cholamine treatment, hemodynamic status remained unsta- ble. Continuous low-dose infusion of terlipressin (2.6 lg d kg-1 d h-1) was initiated as rescue therapy. Terlipressin dramatically improved hemodynamic status without serious
deleterious effects. Continuous low dose of terlipressin could be considered as a rescue therapy in children with purpura fulminans.
Studies and case series showed that infusion of terli- pressin (TP), a long-acting arginine-Vasopressin analogue, can restore hemodynamic and tissue perfusion pressure in adults or children with catecholamine-resistant septic shock [1-4]. However, modality of administration and optimal doses remain poorly defined. We report a case of a child with meningococcal septic shock treated by continuous low doses of TP as rescue therapy.
A 3-year-old, 15-kg girl was admitted in an outside emergency department for purpura fulminans. She immedi- ately received intravenous ceftriaxone sodium. Then, the child was transferred to our pediatric intensive care. On admission, we noted a Glasgow Coma Scale score of 7, mean arterial pressure (MAP) of 31 mm Hg, heart rate (HR) of 179/min, hepatomegaly, and extensive purpura. White blood cell count was 5800/mm3, and platelets were at 60000/mm3. Arterial blood gas analysis showed a metabolic acidosis with a pH of 7.28 and Paco2 of 41 mm Hg. arterial blood lactate level was 2.89 mmol/L. Diuresis was preserved. Serum
creatinine level was 84 lmol/L and blood nitrogen
10.7 mmol/L. Forty milliliters per kilogram of crystalloid solution was transfused. Every 6 hours, 1 mg/kg of hydro- cortisone was prescribed. During the first 6 hours after admission, hemodynamic status worsened. Peripheral Blood lactate levels went to 6.4 mmol/L. Echocardiography showed a normal left ventricle contraction and normal ventricle volumes. Central venous oxygen saturation was 69%. Norepinephrine and dobutamine increase had almost no effect on MAP. Thus, it was decided to use TP as rescue therapy. A continuous infusion of a low dose of TP
(2.6 lg d kg-1 d h-1) was initiated. Fifteen minutes later, an
increase in MAP was observed (Fig. 1). During the 6 hours after the initiation of TP, norepinephrine doses could be
decreased, diuresis increased from 1 to 4 mL d kg-1 d h-1, serum creatinine level fell to 52 lmol/L, and blood nitrogen to 7.5 mmol/L. Venous blood lactate level decreased to
4.2 mmol/L. Ten hours after TP was initiated, venous blood lactate level was 2.0 mmol/L. After 24 hours of treatment, TP was stopped because distal ischemia increased, and a major improvement in hemodynamic status was obtained. Limbs got warmer slowly, and no amputation was needed. Skin lesions regressed, except for 4 small ulcerations, which required local care. The child was discharged from intensive care 11 days later. The responsible bacteria was isolated in blood cultures: a serogroup-B Neisseria meningitidis.
Terlipressin doses during septic shock in children remain unexplored. In previous case reports or series, TP dose was based on doses used in adult studies. Most clinicians used a bolus between 7 and 20 lg/kg and, in one case, continuous infusion between 10 and 20 lg/kg (Table 1). For the first time to our knowledge, such a continuous low dose has been successfully used. Doses of TP 4 times lower than those
previously used were enough to restore hemodynamic status without deleterious effects.
Terlipressin Bolus injection increases vascular resistance and can decrease cardiac output. However, this effect was explained by a decrease in HR, and there were no variations in stroke volume when it was measured [1,2,6]. Using conti-
nuous infusion with 10 lg d kg-1 d h-1, Zeballos et al [8]
Fig. 1 Hemodynamic status progression according to norepi- nephrine and TP administration.
0735-6757/$ - see front matter D 2007
Claude Martin MD De’partement d’Anesthe’sie et de Re’animation Centre Hospitalo-Universitaire Nord
13915 Marseille Cedex 20, France
CI indicates continuous infusion.
4 Treatment was initiated with 7 lg/kg every 12 hours and titrated to 20 lg/kg every 6 hours according to hemodynamic and side effects.
0/1
1
4 2/2
every 4 h
Bolus, 20 lg/kg
every 4 h
CI, 10-20 lg d
kg-1 d h-1
Zeballos 2 mo
et al [8]
Rodriguez-Nunez 1 mo-13 y Bolus, 20 lg/kg 16 7/9
et al [4]
Rodriguez-Nunez 4 mo-6 y et al [7]
1/0
1
11 y
Peters
et al [6]
6/8
14
7 d-17 y
Matok
et al [3]
1 0/1
Bolus,
7 lg/kg
every 12 h
Bolus, 7 to
20 lg/kg
every 6-12 h4
Bolus, 14 lg/kg
every 8 h
Matok 8 d
et al [5]
Table 1 Terlipressin use in pediatric septic shock
Authors Age Doses of TP No. of Alive/dead
cases
doi:10.1016/j.ajem.2007.02.019
References
also observed a decrease in HR. In the present case, we did not observe reduction of HR after TP infusion. Possibly, low- dose continuous infusion slowly modified the postcharge and made HR stability possible. Terlipressin-induced vasocon- striction can lead to disastrous distal ischemia [4,9,10]. In our patient, distal ischemia was increased after TP treatment onset but was associated with blood lactate diminution. Continuous low doses of TP were enough to restore hemodynamic status without causing deleterious effects.
Finally, despite the ischemic phenomenon of purpura fulminans, TP could be used as a rescue therapy when fluid resuscitation and catecholamine infusion fail to improve hemodynamic status. There are no data about the optimal dose to use in children, but treatment could be initiated with continuous low-dose infusion and titrated according to the observed clinical effects. Clinical studies are needed to confirm this observation.
Fabrice Michel MD Laurent Thomachot MD Marion David MD Claire Nicaise MD Renaud Vialet MD
Jean-Noel Di Marco MD Pierre Lagier MD
De’partement d’Anesthe’sie-Re’animation Unite’ de Re’animation Pe’diatrique et Ne’onatale
et Unite’ de Bru^le’s Pe’diatriques Centre Hospitalo-Universitaire Nord 13915 Marseille Cedex 20, France
E-mail address: [email protected]
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