Acute Effects of Intermittent Hemodialysis and Sustained Low-Efficiency Hemodialysis (SLED) on the Pulmonary Function of Patients under Mechanical Ventilation

Abstract

The effects of hemodialysis (HD) on pulmonary function are still controversial. The objective of this study was to evaluate the effect of intermittent hemodialysis (IHD) and sustained low-efficiency dialysis (SLED) on the respiratory mechanics of ICU patients under invasive mechanical ventilation. We prospectively studied 31 patients. Laboratory and respiratory evaluation (static and dynamic compliance and resistance) was performed pre- and post-HD. Forty HD sessions were studied and grouped in: SLED (n = 17; Qa = 200–250 mL/min, Qd = 300 mL/min) and IHD (n = 23; Qa = 250–300 mL/min, Qd = 500 mL/min). There was no difference between the groups according to age, gender, comorbidities, APACHE II, and cause of mechanical ventilation, but pre-HD, patients in the IHD group had higher levels of plasma creatinine (5.4 ± 2.0 vs. 4.2 ± 1.3 mg/dL, p = 0.048) and platelets (286 ± 186 vs. 174 ± 95 10³/mm², p = 0.032) and lower arterial pH (7.37 ± 0.07 vs. 7.42 ± 0.05, p = 0.02). The efficiency of the treatment was similar (p > 0.05) with both types of HD regarding fluid removal, urea reduction rate, and decrease in plasma creatinine. Pre-HD, the ventilatory conditions of both groups were similar (p > 0.05) except for pressure support ventilation and airflow resistance. There were no changes (pre- versus post-HD p > 0.05) induced either by IHD or SLED in the ratio PaO₂/FiO₂ or in any measured ventilatory parameter. In conclusion, neither IHD nor SLED modifies the pulmonary function of patients under mechanical ventilation.

Keywords:

• renal failure
• ICU
• mechanical ventilation
• pulmonary function
• intermittent hemodialysis
• sustained low efficiency dialysis

INTRODUCTION

The intermittent hemodialysis (IHD) has been a useful renal replacement therapy for critically ill patients. Some dialysis membranes (mainly cuprophane) used in IHD induce pulmonary inflammation and consequently can worsen the respiratory function in these patients.[1] On the other hand, by removing fluids, IHD can ameliorate pulmonary congestion and edema and thus improve their respiratory conditions.[2],[3] However, the alterations induced by IHD on pulmonary function of mechanically ventilated patients have been described in few studies using cuprophane membrane.[4],[5] Although less biocompatible than the synthetic membranes, the modified-cellulose membranes are more biocompatible than cuprophane and less expensive than the synthetic membranes.[6],[7]

In critically ill patients, IHD can induce hemodynamic instability and worsen systemic and pulmonary circulation mainly when its prescription is the same used for stable ESRD patients. In order to avoid these problems, sustained low-efficiency dialysis (SLED) has been used in ICU.[8] The objective of this study was to evaluate the changes in the respiratory function of critically ill patients induced by SLED in comparison with the IHD both using low-flux modified-cellulose membranes.

SUBJECTS AND METHODS

Study Design and Setting

This was a prospective study, performed from August 2003 to January 2005, in a five-bed nephrologic ICU of a tertiary-care university hospital. The study was approved by the Ethics Committee of the institution. Written informed consent was obtained from the next of kin. Inclusion criteria included patients mechanically ventilated requiring HD, with an age between 18 and 75 years. Exclusion criteria included patients transferred from other institutions, those who had a tracheotomy, agitated patients not allowing the temporary hyperventilation necessary for measuring respiratory mechanics, the use of ventilator not appropriate for these measurements, and no informed consent.

Definitions

Acute renal failure (ARF) was defined as at least a 25% increase in plasma creatinine when baseline plasma creatinine was ≤ 3.0 mg/dL. Chronic renal failure was when baseline plasma creatinine > 3.0 mg/dL. Acute respiratory failure was PaO₂/FIO₂ < 300 mmHg. Patients were divided according with HD prescription: SLED (n = 17; Qa = 200–250 mL/min, Qd = 300 mL/min) and IHD (n = 23; Qa = 250–300 mL/min, Qd = 500 mL/min).

Patients and Participants

During the study period, 73 patients needing HD and mechanical ventilation were admitted to the ICU. Forty-two patients were excluded for the following reasons: unsuitable ventilator (16 patients), tracheotomy (9 patients), age out of the inclusion range (5 patients), severe hemodynamic instability (3 patients), HD prescription not fitting the protocol (6 patients), and no informed consent (3 patients). Thus, the number of participants was 31, and 40 HD sessions were studied.

Hemodialysis

All HD sessions were performed with a volumetrically controlled ultrafiltration machine, first-use modified-cellulose dialyzer membranes, and bicarbonate dialysate. Patients with no contraindications for anticoagulation received systemic unfractionated heparin; otherwise, the circuit was flushed with saline each 20 minutes. The choice between SLED and IHD prescription was done by the nephrologist on duty according to the patient's need and hemodynamic condition. Net ultrafiltration was calculated as the difference between volume ultrafiltrate and fluid infused into the dialyzer. Urea reduction rate (URR) was calculated a well. Participants were evaluated pre- and post-HD (post-HD: at the HD end or in its fourth hour, whichever occurred first). Pre- and post-HD, the following measurements were taken: arterial blood pressure, cardiac rate, body weight, blood urea, plasma creatinine, arterial blood gas analysis, and respiratory mechanics.

Respiratory Mechanics

The patients used ventilators type Bear 1000 or Bird 8400. Respiratory mechanics was measured by hyperventilation technique in order to eliminate spontaneous respiratory effort [respiratory rate (RR) > 45 bpm by 1 or 2 minutes].[9] Before the measurements, the ventilator was set in controlled volume mode with volume tidal (Vt) = 5 mL/kg, flow of 60 L/minute with a square wave, two seconds of inspiratory pause, RR = 10 ipm, and positive end expiratory pressure (PEEP) = 10 cmH₂O. Measured parameters included plateau pressure (PPLAT), peak airway pressure (PAP), and auto PEEP. Static (Cst,sr) and dynamic (Cdyn) compliance and resistance of respiratory system (Rsr) were calculated by the following equations:

• Cst,sr = Vt/ PPLAT − PEEP total;

• Rsr = PAP - PPLAT / Flow (V´);

• Cdyn = Vt/ PAP − PEEP total;

• PEEP tot = auto PEEP + PEEP set in ventilator.

Ventilator setting, either initial or final HD, was left to the discretion of the physiotherapist on duty in the ICU.

Statistics

Qualitative variables were compared using Fischer`s exact test. Initially, the quantitative variables were evaluated for Gaussian`s distribution using a normality test. According to the normality test, a t-test or Mann-Whitney test was used for comparisons between the groups and paired t-test or Wilcoxon test for comparisons between pre- and post-HD values. The differences of post-HD minus pre-HD values of some variables were calculated. A p < 0.05 was considered statistically significant. Statistical analysis was performed using GraphPad Prism version 4.00 for Windows (GraphPad Software, San Diego, California, USA; http://www.graphpad.com). Continuous variables are expressed as mean ± SD and qualitative variables as %.

RESULTS

Table 1 shows the general characteristics of the 31 participants. All participants were on antibiotic therapy. The reasons for adopting mechanical ventilation had similar distribution in both groups (p = 0.09), with 6 patients in SLED group and 4 in IHD group having acute respiratory failure. No patient had chronic obstructive chronic pulmonary disease. Characteristics of the two modalities of HD are presented in Table 2. Pre-HD body weight was similar in both groups, as well as its decrease induced by the HD. There was a trend (p = 0.06) toward the time between pre- and post-HD to be shorter in IHD (214 ± 43 in IHD and 242 ± 7 minutes in SLED). Moreover, 8 IHD were interrupted before 240 minutes (four times system coagulation, four times hemodynamic instability), but this did not occur in any SLED. Nevertheless, the rate of net ultrafiltration was similar in both groups.

Table 1 General characteristics of the patients

	SLED (n = 16)	IHD (n = 15)
Gender (male: female)	12/4	9/6
Age (years)	52 ± 17	52 ± 16
APACHE II	15 ± 5	13 ± 7
Renal failure
Acute	6	5
Chronic	10	10
Reason for mechanical ventilation
Decreased level of consciousness	5 (31%)	10 (67%)
Others	11 (69%)	5 (33%)
Use of inotropic support	3 (19%)	2 (13%)
Comorbidities
Diabetes mellitus	6 (37.5%)	8 (53%)
Hypertension	6 (37.5%)	7 (47%)
Two or more	8 (50%)	9 (56%)

Abbreviations: SLED = sustained low efficiency dialysis; IHD = intermittent hemodialysis.

Table 2 Characteristics of the hemodialysis sessions

	SLED (n = 17)	IHD (n = 23)
Qa (mL/min)	210 ± 20	296 ± 14
Qd (mL/min)	300	500
Prescribed ultrafiltration (mL)	3429 ± 1165	2743 ± 1422
Net ultrafiltration (mL)	−2137 ± 1266	−2068 ± 1364
Loss of body weight (kg)	−1.8 ± 1.7	−1.5 ± 1.2
Rate of net ultrafiltration  (mL/min)	−8.8 ± 5.2	−9.2 ± 5.5
Anticoagulation	6 (35%)	14 (61%)

Abbreviations: SLED = sustained low efficiency dialysis, IHD =  intermittent hemodialysis, Qa = blood flow rate, Qd = dialysate flow rate.

*p < 0.05 versus SLED.

Pre-HD, the two groups had comparable hemodynamic parameters that remained unchanged post-HD (see Table 3). The same occurred regarding the number and dose of vaso-pressor drugs. The two groups did not differ in the level of hemoglobin, leukocytes, and plasma sodium and potassium. However, SLED had lower platelets levels (174 ± 95 versus 286 ± 186 × 10³/mm³, p = 0.03) than IHD, explaining why in only 35% of SLED sessions, anticoagulation was used. The changes in renal parameters and in arterial blood analysis observed post-HD are shown in Table 4. Pre-HD, the IHD group had lower pH and higher plasma creatinine. However, the improvement in the renal parameters and in arterial pH, bicarbonate, and base excess was similar in both groups. URR was 51 ± 22% in SLED and 44 ± 15% in IHD, p = 0.2531. There was no improvement in PaO₂ or ratio PaO₂/FIO₂ in any group (see Table 4). Analysis of the pre-HD pulmonary parameters showed that IHD had higher pressure support ventilation (PSV). HD did not modify pulmonary parameters in any group. Pre-HD, the respiratory mechanics were similar in both groups, and no significant changes were induced by the procedure in any group (see Table 4).

Table 3 Hemodynamic parameters pre- and post-hemodialysis

	SLED		IHD
	Pre-HD	Post-HD	Pre-HD	Post-HD
Systolic blood pressure (mmHg)	149 ± 24	138 ± 33	153 ± 25	143 ± 34
Diastolic blood pressure (mmHg)	79 ± 15	72 ± 21	85 ± 19	79 ± 20
Cardiac rate (bpm)	85 ± 17	91 ± 14	92 ± 17	94 ± 16

Abbreviations: HD = hemodialysis, SLED = sustained low efficiency dialysis, IHD = intermittent hemodialysis.

Table 4 Pulmonary and renal parameters and measurements of respiratory mechanics pre- and post-hemodialysis

	SLED		IHD
	Pre-HD	Post-HD	Pre-HD	Post-HD
Arterial blood analysis
pH	7.42 ± 0.05	7.44 ± 0.06	7.37 ± 0.07	7.44 ± 0.08
PaCO2 (mmHg)	29.8 ± 4.7	31. ± 5.1	32.5 ± 7.4	32.0 ± 7.2
PaO2 (mmHg)	107.2 ± 26.7	105.1 ± 34.7	100.5 ± 27.4	100.2 ± 27.4
HCO^−3 (mEq/L)	18.9 ± 2.2	21.1 ± 2.2	18.7 ± 3.2	21.2 ± 3.8
BE (mEq/L)	−4.1 ± 2.2	−1.9 ± 2.3	−5.4 ± 3.6	−1.9 ± 3.9
O2 saturation (%)	97.5 ± 1.9	97.2 ± 2.1	96.3 ± 3.3	97.3 ± 1.8
Renal
Blood urea (mg/dL)	151 ± 64	59 ± 25	144 ± 64	81 ± 48
Plasma creatinine (mg/dL)	4.2 ± 1.3	2.2 ± 0.9	5.4 ± 2.0	3.5 ± 1.3
Pulmonary
IP (cmH2O)	14.2 ± 3.1	15.2 ± 2.8	15.2 ± 2.8	14.7 ± 2.3
PSV (cmH2O)	9.4 ± 5.9	9.4 ± 5.9	12.8 ± 2.4	12.6 ± 2.3
Vt (mL/kg)	6.4 ± 1.6	6.4 ± 1.6	5.9 ± 3.0	6.4 ± 2.3
RR patient (ipm)	9.5 ± 5.5	9.5 ± 5.5	6.8 ± 6.0	6.6 ± 5.8
RR ventilator (ipm)	6.3 ± 9.7	6.2 ± 9.7	12.5 ± 9.5	11.3 ± 8.9
PEEP (cmH2O)	10 ± 3	10 ± 3	9 ± 3	9 ± 3
FiO2 (%)	36 ± 7	34 ± 5	33 ± 5	33 ± 4
PaO2/FiO2 (mmHg)	312 ± 106	320 ± 94	304 ± 82	319 ± 97
Respiratory mechanics
Cst,sr (mL/cmH2O)	46.2 ± 13.0	47.1 ± 15.7	41.2 ± 16.1	40.7 ± 15.3
Rsr (cmH2O/L.s^−2)	8.9 ± 2.8	8.9 ± 2.3	11.0 ± 3.3	11.1 ± 4.0
Cdyn (mL/cmH2O)	21.6 ± 5.8	23.0 ± 7.5	18.4 ± 6.3	18.6 ± 5.9
Pplat (cmH2O)	18.9 ± 2.5	18.9 ± 3.3	18.6 ± 3.4	19.4 ± 3.5
PAP (cmH2O)	27.8 ± 3.8	28.2 ± 5.3	29.4 ± 4.3	30.0 ± 4.8

*p < 0.05 versus pre-HD.

†p < 0.05 versus SLED.

Abbreviations: HD = hemodialysis, SLED = sustained low efficiency dialysis, IHD = intermittent hemodialysis, BE = base excess, IP = inspiratory pressure, PSV = pressure support ventilation, Vt = tidal volume per kg body weight, RR = respiratory rate, PEEP = positive end expiratory pressure, FiO₂ = fraction of inspired oxygen, Cst,sr = static compliance, Rsr = resistance of respiratory system, Cdyn = dynamic compliance, Pplat = plateau pressure, PAP = peak airway pressure.

DISCUSSION

It is well known that cuprophane dialysis-membrane induces pulmonary granulocyte sequestration resulting in hypoxemia.[1],[10],[11] However, Lang et al.[12] studied 14 stable ESRD patients, 9 with pre-existing lung disease, and compared the acute effects of cuprophane or polysulfone membrane on their pulmonary function. No relevant changes in spirometric data and resistance measurements were observed regardless of the used membrane. Also, there was no correlation between pulmonary function parameters and interdialytic changes in body weight in that study. However, a comparison of cuprophane with other cellulose-modified dialysis membranes showed that cuprophane induces more complement activation and leukocyte decrease than any other cellulose-modified membrane. There were no differences in these parameters among the cellulose-modified membranes.[13] In the present study, which used low-flux cellulose-modified membranes, no changes in peripheral oxygen saturation or PaO₂/FIO₂ were observed during or post-HD, either in IHD or in SLED.

There are many studies in critically ill patients comparing IHD with hemofiltration or hemodiafiltration and the results are still inconclusive.[14] In almost all studies, patients with chronic renal failure are excluded. However, more and more ESRD patients are admitted to the ICU. Clermont et al.[15] analyzed 1530 admissions to a general ICU and found 57 cases of ESRD (4%). In our study, held in a Nephrologic ICU, 20 of the 31 studied patients (64.5%) had chronic renal failure. Alterations in the respiratory drive, muscular functioning, and gas exchanges resulting in impairment of pulmonary function have been described in stable patients with chronic renal failure. These alterations have been ascribed to uremic toxins, fluid overload, malnutrition, inflammation, etc.[16],[17] HD, removing fluid and uremic toxins, could improve pulmonary function; however, our study does not support this idea.

Although Augustine et al.,[18] in comparing intermittent with continuous dialysis in patients with ARF, observed a decrease in mean arterial blood pressure with IHD, we did not observe this decrease even with both Qa and Qd equal to theirs. No hemodynamic changes were induced either by IHD or SLED (see Table 3). However, it should be pointed out that 35% of IHD were interrupted before 240 minutes. Although IHD were expected to be more efficient, the URR with IHD was similar to that obtained with SLED. These findings showed that, in ICU patients, SLED avoided hemodynamic instability and had the same efficiency of IHD.

Uehlinger et al.[19] studied 191 patients with ARF in ICU and compared IHD and continuous venovenous hemofiltration regarding fluid and nutrition administration, mortality, hemodynamic stability, control of uremia and volume overload, and renal recovery. The authors found no differences between the two treatments in any of the evaluated parameters. However, studies considering the effect of IHD specifically in the pulmonary function of critically ill patients are scarce. To the best of our knowledge, there is no study about the effect of SLED on pulmonary function. Huang et al.,[4] when studying 14 hemodynamically stable patients (most of whom presenting pulmonary congestion or pleural effusion in chest X-ray), did not find significant changes in PaO₂, tidal volume, or respiratory rate after 240 minutes of IHD with cuprammonia rayon membrane. Nevertheless, they observed an improvement in auto PEEP, resistance of respiratory system, and dynamic compliance, and ascribed these findings to the achieved ultrafiltration (the patients lost 2.7 ± 1.4 Kg of body weight). Chen et al.,[5] also studying 14 hemodynamically stable patients, found a decrease in peak airway pressure, plateau pressure, and in the resistance of respiratory system. The last parameter was correlated with the loss of body weight (r = 0.71, p < 0.005). The body weight loss ranged from 0.25 to 4.85 kg. However, the authors did not find any improvement in the static compliance. Our study did not observe significant changes in the resistance of respiratory system or in dynamic or static compliance, perhaps because our patients had lost less body weight: 1370 ± 1500 g.

From our point of view, SLED using modified-cellulose membrane is a very useful renal replacement therapy in ventilated critical patients: it is not as expensive as the continuous methods and avoids hemodynamic instability with an efficiency similar to IHD. In the ICU setting, acute changes in respiratory function (improvement or worsening) induced either by IHD or SLED should not be expected.