Introduction
Septic shock is a disease caused by infection, with
abnormal blood distribution as the main feature, and with the
hypoxic ischemic tissues and organs as the major pathophysiological
changes (1–3). The gastrointestinal hypoxia remains
after the blood pressure is corrected. The early monitoring of
gastric pH can be useful in the diagnosis of the local tissue
hypoperfusion and hypoxia, and application in clinical medication
(4,5). Treatment with vasoactive drugs is an
effective means of relieving ischemia and hypoxia in tissue and
organs.
In the present investigation, of 48 cases with
septic shock, the gastric mucosal pH was monitored when patients
were treated either with dopamine or norepinephrine alone or with
norepinephrine and dobutamine in combination to observe the effects
of vasoactive drugs on gastric pH (6).
Materials and methods
Clinical data
From July 2002 to December 2006, in total 48 cases,
including 32 males and 16 females aged 15–83 years at an average of
48.9 years, were hospitalized and treated with vasoactive drugs for
>2 days at the People's Hospital of Lishui City (Zhejiang,
China). Primary disease included 18 cases of severe pulmonary
infection, 12 cases of abdominal infection, 2 cases of skin
avulsion plus infection in a large surface, 6 cases of severe
pancreatitis, and 5 cases of acute suppurative cholangitis. Two
cases of lower limb infection, and 3 cases of thoracoabdominal
injuries caused by traffic accidents. The 48 cases were divided
into 3 groups, and the gender, age, acute physiology, and chronic
health evaluation, hemodynamic indicators and gastric pH prior to
treatment were not significantly different between the 2 groups
(all at P>0.05).
The diagnostic criteria employed for septic shock
were: i) Patient with clear infected lesions; ii) patients with
systemic inflammatory response; iii) systolic blood pressure of
<90 mmHg (1 mmHg=0.133 kPa), or a decrease in the systolic blood
pressure by 40 mmHg from the original base that did not recover
after 1 h of fluid resuscitation, or decreased systolic blood
pressure recovered and maintained normal only after the patients
were treated with vasoactive drugs; and iv) patients with poor
perfusion in tissues. The patients who met the above criteria were
divided into 3 groups and treated with different vasoactive drugs.
In group A, 16 patients were treated with dopamine (3–15
µg/kg/min). In group B, norepinephrine (0.05–0.50 µg/kg/min) was
used to treat 16 patients. Group C comprised 16 patients who were
treated with dobutamine (2–5 µg/kg/min) plus norepinephrine. The
mean arterial pressure (MAP) of the 3 groups of patients was at
70–80 mmHg for regulating standards, and the patients were treated
with adequate fluid resuscitation before medication.
Observation index
i) A catheter was surgically arranged in the radial
artery to continually monitor the arterial pressure and arterial
blood gas analysis; ii) a floating catheter was inserted into the
right internal jugular vein to monitor the pulmonary capillary
wedge pressure (PAWP), the cardiac output (CO), and the central
venous pressure (CVP); iii) a gastric tension tube (TRI16 F;
Datex-Ohmeda, Helsinki, Finland) was set through the nose to
measure the carbon dioxide partial pressure within the gastric
mucosa (PiCO2), and the pH of gastric mucosa was
calculated according to the Henderson-Hasselbalch equation, pH=6.1
l g [HCO-3]/PiCO2 × 0.03; and iv) the pH of gastric
mucosa prior to medication (baseline) and 6, 12, 24 and 48 h after
administration of hemodynamic changes of each group were observed,
and the hemodynamic changes at 6 h in each group were observed
after treatment.
Statistical analysis
Data were presented as mean ± standard deviation,
processed with SPSS 11.0 software (IBM Corp., Armonk, NY, USA) and
all treatments were subjected to variance analysis. The intergroup
statistical results were compared using the q test and P<0.05
was considered to indicate a statistically significant
difference.
Results
Changes of the gastric mucosal pH
The gastric mucosal pH values were not significantly
different between 2 of the 3 groups prior to treatment (baselines,
each at P>0.05). The gastric mucosal pH of group A did not
change 6, 12, 24 and 48 h after treatment with drugs compared with
the baseline (all at P>0.05), while the gastric mucosal pH in
groups B and C were statistically higher at the time points of 6,
12, 24 and 48 h after treatment with drugs compared with the
respective baselines (all at P<0.05). After treatment with
drugs, the gastric mucosal pH of group C at the time points of 6,
12, 24 and 48 h after treatment were significantly higher than
those of group A and group B at these same time points after
treatment, while there were statistical differences between groups
A and B at the 6, 12, 24 and 48 h time points after treatment (all
P<0.05). The results are shown in Table I.
 | Table I.Gastric mucosal pH of 3 groups before
(baseline) and after medication (mean ± SD). |
Table I.
Gastric mucosal pH of 3 groups before
(baseline) and after medication (mean ± SD).
|
|
| Time points after
treatment |
|---|
|
|
|
|
|---|
| Groups | Baseline | 6 h | 12 h | 24 h | 48 h |
|---|
| A | 7.21±0.21 | 7.23±0.13 | 7.24±0.21 | 7.25±0.22 | 7.25±0.03 |
| B | 7.20±0.25 |
7.27±0.17a |
7.27±0.25a |
7.27±0.02a |
7.28±0.03a |
| C | 7.20±0.23 |
7.37±0.21a,b |
7.37±0.21a,b |
7.37±0.24a,b |
7.38±0.02a,b |
Hemodynamic changes
Hemodynamic indicators of the patients prior to
treatment were not significantly different between 2 of the 3
groups (all at P>0.05). Compared with the baseline values, the
MAP and cardiac index (CI) of each group after treatment were
significantly increased. Following treatment, the PAWP and the CVP
of groups B and C significantly increased (all at P<0.05),
albeit the two parameters of group A changed only insignificantly.
After medication, the heart rate of group A (treated with dopamine)
significantly increased (P<0.05) while the heart rate of the
other 2 groups increased insignificantly. The results are shown in
Table II.
| Table II.Hemodynamic indicators before
(baseline) and 6 h after medication (mean ± SD). |
Table II.
Hemodynamic indicators before
(baseline) and 6 h after medication (mean ± SD).
| Groups | MPA, mmHg | HR, times/min | PAWP, mmHg | CVP, mmHg | CI, l/min |
|---|
| Baseline | 61±8.1 | 116±23.6 | 10.0±2.2 | 7.0±2.3 | 4.0±0.7 |
| A | 76±4.2a | 136±23.5a | 11.4±2.1 | 8.0±2.7 | 5.4±0.8a |
| B | 75±4.9a | 116±16.2 | 14.0±1.8a | 15.0±2.8a | 4.8±1.1a |
| C | 75±5.0a | 118±21.3 | 14.0±1.6a | 14.8±3.0a | 5.5±1.1a |
Discussion
Impact of vasoactive drugs on the
hemodynamics
The results of this study showed that the vasoactive
drugs can raise blood pressure and oxygen delivery levels. In
septic shock patients, cardiac dysfunction at varying degrees
affected myocardial contractility, reduced CO and resulted in
decreased blood pressure (7–9). Vasoactive drugs can increase CO and
blood pressure because they cause the contraction of blood vessels
(10). Norepinephrine mainly affects
α-receptors, increases the cardiac after load, but it shows weak
cardiac effects of β-receptor (11–13). The
patients in group C were treated with norepinephrine and
dobutamine, the MAP, CI, and other hemodynamic parameters were
increased and cardiac function significantly improved. The effect
of β-adrenergic receptors by dobutamine resulted in the expansion
of blood vessels and caused lower blood pressure (14–16).
Therefore, blood pressure can be increased and heart function
improved in patients with septic shock and hypotension if they are
treated with dobutamine at low dose and norepinephrine at normal
dose.
Effects of vasoactive drugs on gastric
pH
The ideal vasoactive drugs are those that can
rapidly raise blood pressure, improve organ perfusion, and increase
gastric mucosal pH.
The choice of vasoactive drugs remains the focus of
academic debate. Currently, norepinephrine plus dobutamine has
become the first medication choice for treatment of septic shock,
they can improve blood perfusion of the whole body, especially the
blood perfusion of internal organs (17,18).
When the shock begins, the use of vasoactive drugs must be taken
into consideration to maintain MAP at 70–80 mmHg if a fluid
resuscitation cannot maintain the blood pressure. As a β-adrenergic
receptor agonist, dobutamine can enhance the myocardial
contractility, increase the CO, reduce the peripheral vascular
resistance, and improve splanchnic blood perfusion (19–21), in
particular, can improve tissue oxygenation and play an antishock
effect by maintaining or increasing the level of oxygen delivery
(DO2) or oxygen uptake of tissues. The possible reason
for norepinephrine playing a role in the increase of the splanchnic
blood delivery and gastric mucosal pH of patients with septic shock
is that the positive inotropic effect of β2-receptor of
norepinephrine caused an increase of CI, DO2 but did not
change the splanchnic blood distribution. Compared with the use of
norepinephrine alone, the use of norepinephrine and dobutamine in
combination can increase CI and gastric mucosal pH significantly
(P<0.05). Investigators considered that this joint effect of
norepinephrine and dobutamine is, based on the increase of CI
followed by the improvement of the splanchnic blood perfusion, but
also based on the improvement of blood circulation in stomach due
to the redistribution of the blood flow in mucous layer of the
stomach wall (22). The results of
the present study showed that the gastric mucosal pH was
significantly increased 6 h after administration of norepinephrine
and dobutamine in combination (group C), but the pH after treatment
with dopamine alone did not clearly change (group A). The reason
may be that the imbalanced supply and demand of local oxygen, or
the shortage of blood supply caused by redistribution and short
circuit of blood flow in gastrointestinal mucous membrane. In this
study, the gastric mucosal pH of the norepinephrine-treated
patients (group B) increased to a certain extent but was
insignificantly different from that of patients treated with
norepinephrine plus dobutamine (group C). The reason for this was
that the strong vasoconstriction effects of norepinephrine may
still affect the visceral blood perfusion (23–25).
The results suggested that the use of norepinephrine
and dobutamine in combination can more effectively improve the
splanchnic perfusion in comparison to the use of dopamine or
norepinephrine alone, and the co-effect of norepinephrine and
dobutamine may be related to the changes of intestinal blood flow
distribution by dobutamine.
Significance of monitoring the pH of
the gastric mucosa
The gastric mucosal pH is a sensitive indicator
reflecting the ischemia and hypoxia of gastric mucosa, suggesting
that successful resuscitation concealed the risk of visceral
ischemia, especially the risk of gastrointestinal ischemia
(26,27). The normal pH value is 7.38±0.03,
while reduced gastric mucosal pH indicated the presence of hypoxia
and hypoperfusion in intestinal tissue. At 2–3 days prior to the
dysfunction of multiple organs, visceral hypoperfusion was evident
(28). The oxygenation obstacles
appeared initially in the gastrointestinal mucosa and the gastric
mucosa recovered later. Sometimes the pH of gastric mucosa is at a
low value after the systemic monitoring indicators have returned to
normal. The low value of the gastric mucosal pH is a recessive
shock (29). At this point, the
patient should be treated continually for resuscitation until the
gastric mucosal pH is corrected. Therefore, the continuous dynamic
monitoring of the pH is important for ischemia of the
gastrointestinal tract. The key points to shock resuscitation are
the improvement of tissue hypoperfusion and the reversing of tissue
ischemia and hypoxia, and the measurements for these purposes are
the use of vasoactive drugs and the addition of blood volume
vasoactive drugs have different effects on gastric mucosal pH
(30). Although lactic acid is a
systemic index for adequacy of tissue perfusion, the blood flow is
not evenly distributed into all types of tissue beds. Local tissues
are subjected to hypoperfusion even though the overall perfusion
index is normal. The gastric mucosal pH is a sensitive indicator
for monitoring the blood perfusion of local tissues of patients
with septic shock (31).
Gastrointestinal ischemia can cause increased gastrointestinal
permeability, the transfer of bacteria and toxins through the
intestinal wall, the release of large amounts of inflammatory
mediators, and lead to sepsis, which is the initiating factor for
multiple organ dysfunction syndromes. It has been found in recent
years that gastric mucosal pH can be used as an important indicator
to test the effective recovery of the shock resuscitation and as a
warning for the complications after resuscitation (32). Thus, the present findings have shown
that the use of vasoactive drugs cannot correct the pH of the
gastric mucosa even if the arterial blood pressure and systemic
hemodynamics have been corrected and the results indicated that the
simple increase of the arterial blood pressure in septic shock is
clearly insufficient, therefore, attention should be paid to
splanchnic perfusion.
Acknowledgements
The present study was supported by the Medical Key
Subject of Science and Technology project in Lishui (Zhejiang,
China), no. 2010ZDXK13.
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