OBJECTIVE To observe the effect of penehyclidine hydrochloride on the treatment of septic shock. METHODS Forty-five patients with a confirmed diagnosis of septic shock were enrolled, and they were randomly and equally divided into 3 groups, namely penehyclidine hydrochloride group, anisodamine group and control group (each n=15). Gastric intramucosal carbon dioxide partial pressure (PgCO2) was determined by gastric mucosa tonometry, partial pressure of carbon dioxide in arterial blood (PaCO2) was determined by blood gas analysis and then gastric-arterial carbon dioxide partial pressure gap [P(g-a) CO2] was calculated prior to medication (0 hour) and 1, 6, 12 and 24 hours after medication respectively. The heart rate, mean arterial pressure (MAP), central venous pressure (CVP), urine volume, central venous oxygen saturation (ScvO2) and prognosis were observed. RESULTS Compared with control group, P(g-a) CO2 decreased significantly (P<0.05, respectively) at each time point after medication, whereas no significant difference in MAP or CVP was seen between penehyclidine hydrochloride group and anisodamine group. No marked change in heart rate was found in penehyclidine hydrochloride group, but it increased significantly in anisodamine group (P<0.05). The number of patients that attained the traditional goal of shock resuscitation was 13 in penehyclidine hydrochloride group, 12 in anisodamine group, and 10 in control group. The incidence of compensated covert shock [gastric mucosa remained ischemic with normalized hemodynamic parameters, namely P(g-a) CO2>or=1.2 kPa] was lower in penehyclidine hydrochloride group and anisodamine group [7.7% (1/13), 16.7% (2/12)] than in control group [60.0% (6/10), P<0.05, respectively], P(g-a) CO2 in patients that attained normal hemodynamic parameters were lower in penehyclidine hydrochloride group and anisodamine group [(0.82+/-0.13) kPa and (0.91+/-0.18) kPa] than in control group [(1.22+/-0.21) kPa, P<0.01 and P<0.05]. The time for attaining the satisfactory goal of shock resuscitation was shorter in penehyclidine hydrochloride group and anisodamine group [(4.21+/-0.82) hours and (5.12+/-1.02) hours] than in control group [(6.51+/-1.22) hours, P<0.05, respectively]. However, the time to attain the satisfactory goal of shock resuscitation was shorter in penehyclidine hydrochloride group than in anisodamine group (P<0.05), but no statistically significant difference was found among other findings. CONCLUSIONS Penehyclidine hydrochloride could significantly improve the microcirculation and compensated covert shock without adverse influence on heart rate, shortening of the time of shock resuscitation, and it might have the possibility of decreasing death rate in patients with septic shock. At present penehyclidine hydrochloride is one of the most promising vasoactive drugs in releasing vasoconstriction of microcirculation in patients with septic shock.