The effect of negative wound pressure therapy on haemodynamics in a laparostomy wound model

Abstract

We have recently shown that negative pressure wound therapy (NPWT) induces a decrease in microvascular blood flow in the small intestinal loop close to the dressing. The effect of NPWT is thus thought to be local. In this study, we investigate whether the application of NPWT in laparostomy affects the haemodynamics. Midline incisions were made in six pigs followed by NPWT at −120 mmHg for 20 minutes. The cardiac output, mean systemic arterial pressure, mean pulmonary artery pressu re, central venous pressure, left atrial pressure and superior mesenteric artery blood flow were recorded. The blood flow in a small branch of the superior mesenteric artery was then recorded under NPWT between −50 and −175 mmHg. Cardiac output was not affected by NPWT [P = not significant (n.s.)]. Neither the mean arterial pressure nor the mean pulmonary artery pressure was affected by NPWT (P = n.s.). Negative pressures of −50, −75, −100 and −125 mmHg did not alter the blood flow in the small branch of the superior mesenteric artery (P = n.s.). After application of −150 mmHg, a significant decrease in blood flow was seen (P < 0·01), while the application of −175 mmHg resulted in only a slight decrease in blood flow (P = n.s.). The effect of NPWT in laparotomy seems to be local and to have no influence on central haemodynamics or the blood flow to the superior mesenteric artery.

Introduction

There is an increasing trend towards managing intra‐abdominal surgical emergencies by leaving the incision open and creating a laparostomy. For patients with abdominal compartment syndrome, wound dehiscence, trauma or intra‐abdominal sepsis, decompression laparotomy may be lifesaving 1, 2, 3. Negative pressure wound therapy (NPWT) has remarkable effects on the healing of chronic and difficult wounds, and has shown good results in the treatment of laparostomy 4, 5, 6, 7, 8. Knowledge of the effects of NPWT in a laparostomy wound is, however, limited.

We have recently shown that NPWT in laparostomy in pigs induces a decrease in microvascular blood flow in the small intestinal wall lying close to the NPWT dressing (9). We also showed that the blood flow could not be restored by inserting layers of paraffin gaze between the intestines and the vacuum source (10). The decrease in blood flow was found to be greater with increasing negative pressure 9, 10. We have also shown that conventional NPWT applied to an open abdomen of a pigs produces areas of petechial bleeding in the small intestinal wall (11). We also showed that the area of petechial bleeding could be significantly reduces by inserting a protective plastic disc between the intestines and the vacuum source. The areas of petechial bleeding in the small intestinal wall were significantly larger following conventional NPWT after 12, 24 and 48 hours, than using NPWT with a protective disc between the intestines and the vacuum source. The protective disc seems to protect the intestines, reducing the amount of petechial bleeding (11).

The aim of this study was to elucidate the haemodynamic effects during NPWT of laparostomy. Six pigs underwent laparostomy and the wounds were treated with NPWT at a negative pressure of −120 mmHg. Haemodynamic parameters, including heart rate, cardiac output, mean systemic arterial pressure, mean pulmonary artery pressure, central venous pressure, left atrial pressure and blood flow in the superior mesenteric artery, were recorded after 1, 5, 10, 15 and 20 minutes. The blood flow in a small branch of the superior mesenteric artery was then recorded at negative pressures between −50 and −175 mmHg.

Methods

Animals

A porcine laparostomy wound model was used. Six domestic landrace pigs with a mean body weight of 70 kg were fasted overnight with free access to water. The experimental protocol was approved by the Ethics Committee for Animal Research, Lund University, Sweden. All animals received humane care in compliance with the European Convention on Animal Care.

Anaesthesia and surgery

Premedication was performed with an intramuscular injection of xylazine (Rompun® vet., 20 mg/ml; Bayer AG, Leverkusen, Germany; 2 mg/kg) mixed with ketamine (Ketaminol® vet., 100 mg/ml; Farmaceutici Gellini S.p.A., Aprilia, Italy; 20 mg/kg). Before surgery, a tracheotomy was performed and an endotracheal tube was inserted. Anaesthesia was maintained with a continuous infusion of ketamine (Ketaminol® vet., 50 mg/ml; 0·4–0·6 mg/kg/hours). Complete neuromuscular blockade was achieved by continuous infusion of pancuronium bromide (Pavulon; N.V. Organon, Oss, the Netherlands; 0·3–0·5 mg/kg/hours). Fluid loss was compensated for by continuous infusion of Ringer's acetate at a rate of 300 ml/kg/hours. Mechanical ventilation was established with a Siemens‐Elema ventilator (Servo Ventilator 300, Siemens, Solna, Sweden) in the volume‐controlled mode (65% nitrous oxide and 35% oxygen). Ventilator settings were identical for all animals (respiratory rate: 15 breaths/minutes; minute ventilation: 8 l/minutes). A positive end‐expiratory pressure of 5 cm H₂O was applied. A Foley catheter was inserted into the urinary bladder through a suprapubic cystostomy. Upon completion of the experiments, the animals were given a lethal intravenous dose (60 mmol) ofpotassium chloride.

Wound preparation for NPWT

A 30‐cm long midline incision was performed on each pig. The V.A.C.® Granu Foam™ abdominal dressing system (KCI, San Antonio, TX) was used. The visceral protective layer was cut to an appropriate size, about 35 cm wide and 35 cm long, extending into the paracolic gutters on both sides. A layer of polyurethane Granu Foam was placed on top of the visceral protective layer between the edges of the wound. The wound was covered with a self‐adhesive polyethylene drape, a track pad was inserted through the drape (all from V.A.C., KCI), and then connected to a vacuum source set to deliver continuous negative pressure.

Haemodynamic measurements

The mean systemic arterial pressure was monitored via a catheter in the left carotid artery. The mean pulmonary artery pressure was monitored via a catheter in the pulmonary artery. Double‐lumen central venous catheters were inserted into the left external jugular vein and the left atrium to record the central venous pressure and left atrial pressure, respectively. A flow probe (CardioMed Trace System, Medi‐Stim AS, Oslo, Norway) was placed around the pulmonary artery to record the cardiac output. The catheter was connected to a cardiac output monitor (Oximetrix 3, Abbot Laboratories, North Chicago, IL). The haemodynamic data were collected in a data acquisition system (PowerLab, AD Instruments Ltd., Castle Hill, Australia). The electromagnetic flow metre probes (model BL 613; Biotronex Laboratory Inc., Chester, MD) were positioned around the proximal part of superior mesenteric artery and around a small branch of the superior mesenteric artery leading to the small intestinal loop close to the NPWT dressing. Calibration of the probes was checked in vitro at the end of each experiment. After surgical preparation, the animal was allowed to stabilise for 1 hour. Baseline measurements of the above‐mentioned haemodynamic parameters were made before applying NPWT (0 min). Negative pressure was applied, and the effects on the haemodynamic parameters were recorded after 1, 5, 10, 15 and 20 minutes of NPWT of −120 mmHg.

The animal was once again allowed to stabilise for 1 hour. Negative pressures of −50, −75, −100, −125, −150 and −175 mmHg were then applied, and the effects on the blood flow in a small branch (to the loop segment of the small intestinal wall located close to the NPWT dressing) of the superior mesenteric artery were recorded after approximately 2 minutes of NPWT (steady state). The negative pressures were applied in a random order, at intervals of 10 minutes without any pressure.

Calculations and statistics

Calculations and statistical analysis were performed using GraphPad 5·0 software (San Diego, CA). The effect of NPWT on each haemodynamic parameter was calculated as a percent of the baseline value. Statistical analysis was performed using the Mann–Whitney test when comparing two groups. Significance was defined as P < 0·05 (*), P < 0·01 (**), P < 0·001 (***) and P > 0·05 (not significant – n.s.). All differences referred to in the text have been statistically verified. Values are presented as means ± the standard error on the mean.

Results

Cardiac output (baseline 2·7 ± 0·2 l/minutes, after 20 minutes 2·8 ± 0·2 l/minutes) and heart rate (baseline 78 ± 7 beats/minutes, after 20 minutes 80 ± 5 beats/minutes) were not affected by NPWT (P = n.s., Figure 1). A tendency towards an increase was seen after 1 minute, but the initial values were restored after 5 minutes.

Figure 1.

Cardiac output and heart rate before negative pressure wound therapy was applied (baseline), and 1, 5, 10, 15 and 20 minutes after a negative pressure of −120 mmHg was applied. The results are shown as means ± the standard error on the mean of six experiments. Statistical analysis was performed using the Mann–Whitney test. Significance was defined as P < 0·05 (*), P < 0·01 (**), P < 0·001 (***) and P > 0·05 (not significant). Note the slight increase after 1 minute; the initial values were restored after 5 minutes.

NPWT did not alter the systemic vascular resistance. The pulmonary vascular resistance was not altered (Figure 2). Negative pressure treatment did not alter the central venous pressure (baseline 3·5 ± 0·5 cm H₂O, after 20 minutes 3·0 ± 0·5 H₂O) or the left atrial pressure (baseline 6 ± 1 mmHg, after 20 minutes 5 ± 1 mmHg) (P = n.s., Figure 2), however, a tendency towards a decrease was seen after 1 minute; the initial values being restored after 20 minutes.

Figure 2.

Central venous pressure and left atrial pressure before negative pressure wound therapy was applied (baseline), and 1, 5, 10, 15 and 20 minutes after a negative pressure of −120 mmHg was applied. The results are shown as means ± the standard error on the mean of six experiments. Statistical analysis was performed using the Mann–Whitney test. Significance was defined as P < 0·05 (*), P < 0·01 (**), P < 0·001 (***) and P > 0·05 (not significant). Note the slight decrease seen after 1 minute; the initial values were restored after 20 minutes.

Neither the mean arterial pressure (baseline 100 ± 6 mmHg, after 20 minutes 99 ± 7 mmHg) nor the mean pulmonary artery pressure (baseline 15 ± 1 mmHg, after 20 minutes 14 ± 1 mmHg) was affected by NPWT (P = n.s., Figure 3). A tendency towards an increase was seen after 1 minute, but the initial values were restored after 5 minutes. Negative pressure treatment did not alter the blood flow in the superior mesenteric artery (baseline 136 ± 13 ml/minutes, after 20 minutes 125 ± 9 ml/minutes) (P = n.s., Figure 3), however, a slight decrease was seen over time.

Figure 3.

Mean arterial pressure (MAP), mean pulmonary pressure (MPAP) and superior mesenteric artery blood flow before negative pressure wound therapy was applied (baseline), and 1, 5, 10, 15 and 20 minutes after a negative pressure of −120 mmHg was applied. Note the slight increase in MAP and MPAP after 1 minute; the initial values were restored after 5 minutes. Note also the slight decrease in the superior mesenteric artery flow over time. The results are shown as means ± the standard error on the mean of six experiments. Statistical analysis was performed using the Mann–Whitney test. Significance was defined as P < 0·05 (*), P < 0·01 (**), P < 0·001 (***) and P > 0·05 (not significant).

Negative pressures of −50, −75, −100 and −125 mmHg did not alter the blood flow in the small branch of the superior mesenteric artery (P = n.s., Figure 4). After the application of −150 mmHg a significant decrease in blood flow was seen (P < 0·01, Figure 4), while the application of −175 mmHg resulted in only a slight decrease in blood flow (P = n.s., Figure 4).

Figure 4.

The figure shows the change in blood flow in a small branch of the superior mesenteric artery before (baseline), and after the application of −50, −75, −100, −125, −150 and −175 mmHg. The results are shown as means ± the standard error on the mean of six experiments. Statistical analysis was performed using the Mann–Whitney test. Significance was defined as P < 0·05 (*), P< 0·01 (**), P< 0·001 (***) and P> 0·05 (not significant). Note the significant decrease in blood flow after the application of −150 mmHg, and the slight decrease after the application of −175 mmHg.

Discussion

Critically ill surgical patients frequently develop intra‐abdominal hypertension leading to abdominal compartment syndrome with subsequent high mortality. Among several temporary abdominal closure systems, NPWT has shown improved clinical results, with faster abdominal closure rate and earlier discharge from the intensive care unit compared with similar patients treated with other forms of temporary abdominal closure systems 12, 13, 14, 15, 16, 17.

NPWT therapy has developed from the standard surgical procedure of vacuum‐assisted drainage to remove blood or serous fluid from a wound or surgical site 18, 19, 20. In laparostomy, one important way in which NPWT promotes healing is thought to be by the removal of excessive fluid and exudate. The exudate in a wound may impede the wound healing process as it contains elevated levels of inflammatory cytokines and proteolytic enzymes, as well as low amounts of growth‐promoting cytokines. NPWT allows continuous removal of wound fluid, thus preventing the accumulation of inhibitory factors (21). In a recent study on eight adults receiving NPWT for pressure ulcers, it was shown that the levels of tumour necrosis factors‐α in the wound fluid decreased significantly during the first 24 hours of treatment, and that this decrease was sustained after 7 days. Removing wound exudate by NPWT, thereby optimising the microenvironment of the wound, most certainly has a positive influence on the healing process (22).

Recently, we have shown that NPWT in laparostomy in pigs induces a decrease in microvascular blood flow in the small intestinal wall lying close to the NPWT dressing (9). The decrease in blood flow was seen in the small intestinal loops placed both at the anterior abdominal wall and directly beneath the vacuum source. We also showed that the blood flow could not be restored by inserting layers of paraffin gaze between the intestines and the vacuum source (10). The decrease in blood flow seemed to be greater with increasing negative pressure 9, 10. We have also shown that conventional NPWT applied to an open abdomen of a pigs produces areas of petechial bleeding in the small intestinal wall (11). We also showed that the area of petechial bleeding could be significantly reduced by inserting a protective plastic disc between the intestines and the vacuum source. The areas of petechial bleeding in the small intestinal wall were significantly larger following conventional NPWT after 12, 24 and 48 hours, than using NPWT with a protective disc between the intestines and the vacuum source. The protective disc seems to protect the intestines, reducing the amount of petechial bleeding (11). The area of petechial bleeding may represent areas of ischemia, which might promote the development of fistulae.

We have previously shown that NPWT induces an increase in the blood flow of the peristernal soft tissue (i.e. skeletal muscular and subcutaneous tissue), and also that the change is related to local effects, because the blood flow 4·5 cm from the wound edge was not affected by the negative pressure (23). The blood flow increased with increasing subatmospheric pressure in both subcutaneous and skeletal muscular tissue. When the area under the flow–distance curve (covering a distance of 0·5–4·5 cm from the wound edge) was analysed, a maximal net increase in the blood flow in muscular tissue was observed at pressures of −75 and −100 mmHg (23). A difference was observed in the profiles of the blood flow responses in the subcutaneous and the muscular tissues. The distance from the wound edge to the point at which the blood flow increased was shorter in muscular tissue than in subcutaneous tissue. This may indicate that pressure is transduced differently in dense soft tissue, and that a less dense tissue collapses more easily when subjected to pressure. A zone of relative hypoperfusion was observed in the immediate proximity of the wound edge (23). This zone was larger at high negative pressures, and was especially prominent in subcutaneous tissue. The size of the hypoperfused zone depended on the pressure applied, and expanded with increasing negative pressure. The changes in the peristernal wound blood flow caused by NPWT vary with the distance from the wound edge. A few centimetres away from the wound edge, the blood flow increased when subatmospheric pressure was applied. Conversely, in the immediate proximity of the wound, the negative pressure induced relative hypoperfusion (23). These physiological events may also take place in the intestinal wall during exposure to negative pressures, leading to an ischaemic zone in the intestinal wall that is in close contact with the NPWT dressing.

In this study, we investigated whether the application of NPWT in laparostomy induced any changes in the central haemodynamics. Cardiac output and heart rate were not affected by NPWT. However, a slight increase was seen after 1 minute; the initial values being restored after 5 minutes. When the negative pressure is activated the anterior abdominal walls are drawn together. This may induce an adrenal response that could explain the slight increase in heart rate and secondary increase in cardiac output, and their restoration after a few minutes, when the negative pressure has become stabilised in the abdomen. The same pattern was seen in the mean arterial pressure and the mean pulmonary artery pressure, and may also be explained by an initial adrenal response. However, the increase was not significant, and the analysis is unsure.

The results showed that NPWT did not alter the systemic vascular resistance or the pulmonary vascular resistance; furthermore, neither the central venous pressure nor the left atrial pressure was altered. Negative pressure treatment did not significantly alter the blood flow of the superior mesenteric artery; however, a slight decrease was seen over time. Negative pressures between −50 and −125 mmHg did not alter the blood flow in the small branch of the superior mesenteric artery leading to the intestinal loop close to the NPWT dressing. After the application of −150 mmHg a significant decrease in blood flow was seen, while the application of −175 mmHg induced only a slight decrease in blood flow, which was not significant.

We choose a none pathologic situation on healthy pigs to be able to differentiate the effects from each other when using an infectious model with sepsis and possible unstable haemodynamics. The result of this study indicates that the central haemodynamics are unchanged when NPWT are applied to the open abdomen. We believe that the effect of NPWT is local, but might affect the blood flow to the small branches of the superior mesenteric artery (SMA) leading to the intestinal loop located close to the vacuum source at high negative pressures (−150 mmHg) These results confirms the results published by Brenninger et al. They have showed unchanged pulmonary pressure and blood pressure parameters between primary abdominal closure and NPWT with different negative pressures (−50, −100 and −150 mmHg) when increasing intra‐abdominal volume using a prefilled bag up to 3000 ml water (24). We believe that the haemodynamics remain unchanged after application of NPWT to the open abdomen even in clinical settings. The effect of NPWT would probably not affect the haemodynamics in clinical settings with infection. However, in case of haemodynamic instability and low blood pressure, during sepsis, for example, a decrease in the blood flow to the small branches of SMA could be more obvious at lower negative pressures, however, the actual conclusion could conducted from this study.

Conclusions

In this study, we investigated whether NPWT induced any changes in the central haemodynamic system. We measured cardiac output, heart rate, mean arterial pressure, mean pulmonary artery pressure, systemic vascular resistance, pulmonary vascular resistance, central venous pressure, left atrial pressure and the blood flow in the superior mesenteric artery. None of these parameters was significantly affected, indicating that NPWT acts locally we believe that NPWT of the open abdomen has no influence on central haemodynamics.

Acknowledgement

This study was supported by the Crafoord Foundation and Region Skåne.