Anisodamine Critically Ill SeptIc Shock
Anisodamine Critically Ill SeptIc Shock
Anisodamine has been widely used in China for its pharmacological effect on improving
 microcirculation during shock. It has been reported that anisodamine is effective in reducing
 mortality rate in children with meningitis. however, its effectiveness in patients with
 septic shock has not been systematically investigated. The aim of the study is to investigate
 the effectiveness of anisodamine in the treatment of patients with septic shock.
Septic shock is an important contributor of mortality in the intensive care unit (ICU). The
 crude mortality is reported to be from 30% to 65% (1-5). Although there are significant
 advances in the management of septic shock in recent decades, the mortality rate was only
 marginally reduced. For example, the CUB-Réa Network study reported that the mortality rate
 of septic shock declined from 62.1% in 1993 to 55.9% in 2000 (6). The well-known Surviving
 Sepsis Campaign has also made every effort to reduce mortality rate of severe sepsis and
 septic shock. The organization recommended bundled strategies including early goal directed
 therapy (EGDT) for the management of septic shock (7,8). Although EGDT was once the mainstay
 therapy of septic shock, its efficacy has been questioned by recent several large randomized
 controlled trials (9,10). Therefore, the treatment of septic shock is still a global
 challenge and there is no well-established intervention that can reduce its mortality.

 Anisodamine is an active agent isolated from a Chinese herb medicine. Both experimental and
 clinical studies have shown some potential beneficial effects of anisodamine in improving
 outcomes of shock (11-13). It was reported that anisodamine could reduce the mortality rate
 of fulminant epidemic meningitis from 66.9% to 12.4% (14). The efficacy of anisodamine might
 be mediated via the inhibition of thromboxane synthesis, granulocyte and platelet aggregation
 (15). Although anisodamine has been widely used in the treatment of septic shock in mainland
 China, there is no solid evidence from well designed clinical trials to support its efficacy.
 The aim of the study is to investigate the effectiveness of anisodamine in the treatment of
 critically ill patients with septic shock.
Inclusion Criteria:

 -  patients with septic shock

 Inclusion criteria included patients with sepsis plus use of vasopressors. Systemic
 inflammatory response syndrome (SIRS) is defined as meeting at least one of the following 3
 criteria for a systemic inflammatory response. One of the SIRS criteria must be either the
 WBC criteria (a) or the body temperature criteria (b):

 1. White blood cell count >12,000 or <4,000 or >10% band forms

 2. Body temperature >38oC (any route) or <36oC (accepting core temperatures only;
 indwelling catheter, esophageal, rectal)

 3. Heart rate (> 90 beats/min) or receiving medications that slow heart rate or paced
 rhythm.

 Suspected or documented infection included the following sites: thorax, urinary tract,
 abdomen, skin, sinuses, central venous catheters, and bacterial meningitis.

 Septic shock was defined as sustained arterial hypotension with systolic blood pressure
 (SBP) < 90 mm Hg, mean arterial pressure (MAP) < 70 mm Hg, or an SBP decrease > 40 mm Hg,
 despite adequate fluid resuscitation. To ease clinical screening process, we defined septic
 shock as the requirement of vasopressors despite adequate fluid resuscitation. Vasopressors
 include norepinephrine, epinephrine, phenylephrine and dopamine>5mcg/kg/min.

 Patients with following conditions will be excluded:

 1. Age<15 years old

 2. Moribund (expected to die within 24 hours)

 3. Stay in ICU for more than 24 hours

 4. Contraindications to anisodamine: elevated intracranial pressure, acute phase of
 intracranial hemorrhage, glaucoma, untreated bowel obstruction (surgically treated
 obstruction is not contraindicated), enlargement of prostate without urinary
 catheterization.