Eur Surg Res 1991;23:123-129
© 199! S. Karger AG, Basel 0014-312X/91/O232-0123S2.75/0
Treatment of Hemorrhagic Shock with Intraosseous or Intravenous Infusion of Hypertonic Saline Dextran Solution A. Chavez-Negretea , S. M ajluf Cruz*, A. Frati Munari*. A. Perchesb , R. Argueroc “Department of Internal Medicine, bDepartment of Gastroenterology, d ep a rtm en t of Heart Surgery, La Raza Medical Center, IMSS, Mexico City, Mexico
Key Words. Hemorrhage • Hypertonic saline • Hypotension • Hypovolemia • Shock • Intraosseous infusion • Hyperoncotic solution
Gastrointestinal hemorrhage is one of the commonest causes of emergency room ad mission in the world [1], Mortality due to this cause ranges from 9 to 29% in North America [2] and it is up to 65% if the bleed ing is due to esophageal varices [3], In these cases, quick large intravenous fluid infusions
are required and the infusion of equally ef fective rapidly infused low-volume solution should be advantageous. Hypertonic hyper oncotic solution (7.5% NaCl/dextran 70) has been found effective in resuscitating animals from hemorrhagic shock, even in volumes as low as 4 ml/kg [4, 5]. Holcroft et al. [6, 7]
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Abstract. The efficacy of intravenous or intraosseous infusion of 250 ml of 7.5% NaCl and 6% dextran 60(H/H) was compared with intravenous Ringer’s lactate (RL) for the initial treatment of patients with hemorrhagic shock due to upper gastrointestinal bleeding. 49 patients were randomly assigned to receive either H/H (n = 26) or RL (n = 23). In the first 16 patients with H/H and in all RL patients, solutions were infused by the intravenous route, while the intraosseous route through sternal puncture was chosen for the last 10 H/H sub jects. H/H patients were analyzed together since no differences were noticed between the routes of infusion. The H/H group also received 2.3 ± 0.7 liters of intravenous cristalloid solutions in the first hour and 4.4 ± 0.1 liters in the 24-hour period, while RL received 3.3 ± 0.7 and 7.3 ± 2.4 liters, respectively. Blood pressure (BP) increased during the first 15 min in the H/H group (from 61 ± 17/30 ± 12 to 85 ± 30/48 ± 14 mm Hg) and thereafter, while remaining unchanged in the RL group (from 75 ± 18/40 ± 12 to 75 ± 17/40 ± 14 mm Hg; p < 0.05). The differences between groups were significant throughout 24 h. Urine output and improvement of the Glasgow Coma Score were also higher in H/H patients than in the control group (p < 0.05). There were 5 deaths in RL group and 1 in the H/H group. Sternal of peripheral vein infusion of 250 ml of 7.5% NaCl/6% dextran 60 is an effective initial treat ment of hemorrhagic shock.
124
Châvez-Negrete/Majluf Cruz/Frati Munari/Perches/Argüero
Table 1. Clinical data on entry H/H (7.5% NaCl/6% dextran 60) — i.v (n = 16)
i.o (n = 10)
Age, years Mean Range
42 22-76
41
44
42 52-58
Gender (M/F)
18/8
10/6
8/2
14/9
Blood pressure Systolic, mm Hg Diastolic, mm Hg
64 ±21 32± 14
56 ±18 17± 10
63 ±20 33 ±17
75 ± 18 40 ±12
Heart rate
113 ± 15
119 ± 16
109 ±13
112 ± 19
Hb. g/dl
8.6 ±2
8.2 ± 2
9.4±2
8.6 ± 3
Hct, %
29 ± 6
29 ±7
30 ±5
27 ± 8
9±2
9±2
9± 1
!0 ± 1
9 7 -
3 4 3
9 14 -
Glasgow Coma Score Etiology of bleeding Peptic ulcer Esophageal varices Others
12 11 3
reported improved blood pressure and sur vival with hypertonic saline/dextran solu tion in severely injured patients. Also in pa tients with hemorrhagic shock, wide intrave nous catheters are needed. However, the in sertion of wide catheters is not always easy in patients with hypovolemia and collapsed pe ripheral veins [8]. This problem can be solved using alternative routes to infuse fluids. Intraosseous infusion has been pro posed as an alternative route to reach the blood stream since it provides a rapid vascu lar access [9], This is a prospective, controlled study which evaluates the administration of hypertonic/hyperoncotic (H/H) solutions through the intravenous or intraosseous route in the management of hemorrhagic shock due to gastrointestinal bleeding.
Patients and Methods Adult patients with acute gastrointestinal hemor rhage and arterial hypotension were selected from the Emergency Room of Gastroenterology and Internal Medicine Departments. Inclusion criteria were: (a) systolic blood pressure equal or lower than 90 mm Hg for less than 1 h; (b) normal electrocardiogram, and (c) written consent by the patients or if it was not possible by a first-degree relative. Patients were not included when pregnancy, renal, cardiac or neurolog ical diseases were present. 49 consecutive patients were assigned by random numbers to be treated either with 250ml of 7.5% NaCl/6% dextran 60 solution (H/H) (Schiwa GmbH, Glandorf, FRG) (group 1) or conventional lactated Ringer’s (LR) (group 2). H/H has an osmolality of 2,400 mosm/1 while LR has 276 mosm/1. All solutions were administered as soon as possible (on admission or few minutes after the begin ning of bleeding if patients were already hospitalized) by peripheral vein in the first 16 patients of group 1 and in all patients of group 2, while the intraosseous route was used in the last 10 patients with H/H. When
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total (n = 26)
LR i.v. (lactated Ringer's) (n - 23)
Hypertonie Saline Dextran in Hemorrhagic Shock
the intraosseous route was chosen, a 1.5-cm deep ster nal puncture was performed with a 14-gauge needle which was inserted between the second and third intercostal space [9]. At the end of H/H or Ringer lactate infusion, sup plemental isotonic saline fluid was administered through the peripheral vein in both groups as neces sary in order to achieve a systolic blood pressure higher than 100 mm Hg. In addition, dextran 40 was administered to the control group if necessary accord ing to medical judgement. Packed red cells were transfused if bleeding or hypotension was present after the first 15 min of treatment, or if they reap peared within the next 24 h. Also, standard etiological treatment was carried out in every case (e.g. patients with esophageal varices required a Sengstaken-Blakemore tube, those with peptic ulcer received antacid and cimetidine). Blood pressure, heart rate, Glasgow Coma Score at 15, 30 and 60 min and 4, 8 and 24 h were recorded. Blood count, BUN, serum creatinine, and serum electrolytes and arterial gases were deter mined at arrival and at 24 h. All data in figures and tables are presented as mean ± SD. Statistical methods were analysis of vari ance and paired Student’s t test, p < 0.05 was consid ered significant. The study was approved by the Hos pital Ethical-Investigation Committee.
125
Fig. 1. Blood pressure after H/H infusion of up to 24 h by peripheral vein (n = 16; •), intraosseous route (n « 10; o) and LR group (n = 23; o). A significant difference was noticed (p < 0.05) between the H/H group and control group at 15 min after infusion. No differences were found between intraosseous or intra venous infusion in the H/H group. For clarity pur poses, only mean values are shown.
Fourty-nine patients were studied: 26 re ceived H/H through the peripheral vein (16 patients) or by the intraosseous route (10 patients) while 23 individuals were in the control group with LR. There were no differ ences in initial demographic or clinical data, or blood pressure, pulse rate or therapeutic response between patients who received H/H solution by the peripheral vein or by the intraosseous route. Thus they were further analysed as a whole group. On entry, age, gender, blood pressure, heart rate, Glasgow Coma Score, hematocrit as well as the etiol ogy and site of hemorrhage were similar in group 1 and 2 (table 1). A nearly identical
significant increase in BP was noted 15 min after sternal or intravenous infusion of H/H (63 ± 21/33 ± 17/91 ± 20/50 ± 20 and 61 ± 17/30 ± 12 to 85 ± 30/48 ± 14 mm Hg, respectively). Blood pressure rose from 15 min on and thereafter with the infusion of H/H with sta tistical significance (p < 0.05) as compared with the control group (fig. 1). Hypotension persisted for at least 1 h in several patients of the control group despite rapid infusion of intravenous fluids. Patients of group 1 re ceived 2,360 ± 723 ml of cristalloid solu tions in the first hour, while subjects of group 2 received 3,312 ± 750 ml in the same
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Results
Chavcz-Negrete/Vlajluf Cruz/Frati Munari/Perches/Argiiero
Fig. 2. Heart rate values after H/H (intraosseous and peripheral vein; n - 26; •) vs. LR group (n = 23; o). Bars indicate the SD. Differences between groups were not significant (p > 0.05).
period. Heart rate decreased throughout the 24 h in both groups, without difference be tween groups (fig. 2). 24-Hour urine output was higher in group 1 than in group 2 although group 1 re ceived only 4,400 ± 188 ml of supplemental fluids in 24 h while in group 2 7,300 ± 2,400 ml were infused in the same period (fig. 3). Serum electrolytes at the time of en try and after 24 h were within normal limits in both groups (data not shown). The amount of packed red cells transfused was also higher in controls (950 ± 500 ml) than in the H/H group (480 ± 200 ml p < 0.05). Most patients of group 2 received two or more units of packed red cells while only 7 subjects of group 1 received two or three units (table 2). In spite of transfusions, only
Fig. 3. 24-Hour urine output af ter H/H (intraosseous and periph eral vein) infusion vs. LR group (p < 0.05) and supplemental fluids in both groups (p = NS).
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126
127
Hypertonie Saline Dextran in Hemorrhagic Shock
a mild nonsignificant improvement of ane mia was noticed at 24 h in both groups which reflects the magnitude of the hemor rhage. On entry, pa02 was lower in the H/H group than in the control group; however, it rose close to normal limits in the following 24 h (table 3). A significant improvement of neurological status was also noticed in H/H patients reaching statistical significance at 24 h (p < 0.05) (fig. 4). The improvement was best noticed in those patients with an initial Glasgow Coma Score lower than 10 (table 4). Within the 24 h of the study, 5 patients died in the control group while only 1 died in the H/H group.
Table 2. Packed red cell requirement Solutions
7.5% NaCl/6% dextran 60 Lactatcd Ringer’s
Units (300 ml) 0
1
2
4 0
15 1
6 13
3 >4 1 3
0 6
Fig. 4. Glasgow Coma Score at entry and after 24 h in patients receiving H/H (7.5% NaCl/6% dextran 60) or LR (lactatcd Ringer’s). Though improve ment was seen in both groups, it was significant only in the H/H group (p < 0.05, Mann-Whitney U test). The differences between the number of patients who improved in H/H vs. LR were also significant (p < 0.02, Fisher’s test).
Table 3. Arterial blood gases Entry
1h
24 h
pH
H/H LR
9 6
7.37 + 0.3 7.36±0.4
7.4 ±0.8 7.34±0.7
7.42 ±0.6 7.36±0.2
pCOi, mm Hg
H/H LR
9 6
17.8 ±1.04 34.1+2
20.8 ±4 34.6 ± 1
23.27 ±2.2* 35.2 ±1.4
pO;, mm Hg
H/H LR
9 6
44.5 ± 15 61.5 + 5
HCOt, mEq/1
H/H LR
9 6
11.9 ± 2 18.6 ± 7
Results expressed as X ± SD. * p < 0.05: entry vs. 24 h later. No mechanical ventilation was used (FI0., 21 %).
65± 16 69 ± 18 14.4 ±2 22 ±2
67± 17* 62 ±4 17.2 ±4* 22 ±8 Downloaded by: Univ.of California Berkeley 128.32.10.230 - 7/26/2018 10:20:31 AM
n
128
Table 4. Glasgow Coma Score Solution
n
Entry Score after score 24 h X ± SD
7.5% NaCl/6% dextran 60
10 6
< 10 + 5.5+ 1.4* > 10 + 2.16 ± 0.4
Lactatcd Ringer’s
0 ± 0 .5 b 10 < 10 6 > 10 +1.9 ± 1.5
* p < 0.05 a versus b.
Discussion Velasco et al. [10] reported in 1980 that 4 ml/kg of 7.5% NaCl solution was effective in resuscitating animals from hypovolemic shock. Later, Smith et al. [11] found that the combination of 7.5% sodium chloride with 6% dextran 70 was more effective than hy pertonic saline alone; this solution also re stored acid-base balance, urine output and tissue oxygen consumption in hypovolemic animals [12], Holcroft et al. [6, 7] showed that a similar hypertonic/hyperoncotic solu tion (7.5% saline/4.2% dextran 70) en hanced blood pressure in severely injured patients. In this study, H/H solution was effective in patients with severe hemorrhage restoring blood pressure within few minutes, and the beneficial effect lasted for the next 24 h. Re markably, in the control group, blood pres sure did not immediately rise in spite of large volume replacement. The immediate hemodynamic effects of H/H solution can be ascribed to its hyperosmolality, which causes plasma volume expansion [13], enhance ment of myocardial contractility [14] and higher blood pressure, leading to a rise of
organ blood flow [12, 15]. In this study, blood pressure increased as well as urine out put. The last may be the result from both higher renal blood flow [16] and osmotic diuresis. The improvement in arterial pCL after H/H may be a consequence of better hemodynamic conditions. Neurological improvement measured by the Glasgow Coma Score that was noticed mostly in patients treated with H/H solution was consistent with the overall clinical sta tus. Although we did not measure intracra nial pressure, it is noteworthy that in experi mental animals, resuscitation from hemor rhagic shock with isotonic fluids resulted in enhancement of intracranial pressure while hypertonic fluids maintain low intracranial pressure [17, 18], Intraosseous injection of H/H has been proposed as a rapid means of gaining vascu lar access when peripheral cannulation is dif ficult [9], Intraosseous infusion is easy to per form and does not require special training. In the present study, 10 patients were injected into the sternum with 250 ml of H/H without complications. Volume expansion with this method was as rapid and effective as periph eral vein infusion. This method may be use ful in emergencies if peripheral veins are not readily accessible. In this study, no complica tions ascribed to H/H solution or to intraos seous sternal infusion were seen. It is known that conventional therapy and emergency surgery have failed to reduce the overall mortality of bleeding from esophageal varices [19], Likewise, in this study, mortal ity was due to hemorrhage from esophageal varices in all the cases. In the H/H group there was only 1 death, while there were 5 deaths in the control group, although both groups were similar in initial clinical status, hematocrit and cause of bleeding. Further
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Chávez-Negrete/Majluf Cruz/Frati Munari/Perches/Argüero
Hypertonie Saline Dextran in Hemorrhagic Shock
References 1 Gostout CJ: Acute gastrointestinal bleeding - A common problem revisisted. Mayo Clin Proc 1988;63:596-604. 2 Halmagyi AF: A critical review of 425 patients with upper gastrointestinal hemorrhage. Surg Gy necol Obstet 1970;130:419-430. 3 Westaby D, Macongall B, Williams R: Improved survival following injection sclerotherapy for esophageal varices. Final analysis of a controlled trial. Hepatology 1985;5:827-830. 4 Kramer GC, Perron PR. Lindsey DC. et al: Smallvolume resuscitation with hypertonic saline dextran solution. Surgery 1986;100:239-246. 5 Maningas PA, De Guzman LR, Tillman FJ, et al: Small volume infusion of 7.5% NaCI in dextran 70 for the treatment of severe hemorrhagic shock in swine. Ann Emcrg Med 1986; 15:1131-1137. 6 Holcroft JW, Vassar MJ, Tunncr JE, et al: 3% NaCI and 7.5% NaCl/dextran 70 in the resuscita tion o f severely injured patients. Ann Surg 1987; 206:279-286. 7 Holcroft JW, Vassar MJ, Perry CA, et al: Perspec tives on clinical trials for hypertonic saline/dextran solutions for the treatment of traumatic shock. Brazilian J Med Biol Res I989;22:291293. 8 Smith Jp, Bosai BI, Hill AS, Frey CF: Prehospital stabilization of critically injured patients: A failed concept. J Trauma 1985;25:65-70. 9 Saavedra J, Patterson HA, Kramer GC: Intraos
10
11
12
13
14
15
16
17
18
19
seous injection of hypertonic saline dextran. Ana tomic considerations in man and sheep. Circ Shock 1988;24:283. Velasco LT, Pontieri V, Rocha-e Silva M Jr. Lopez OU: Hyperosmotic NaCI and severe hemorrhagic shock. Am J Physiol 1980;239:H664-H673. Smith GJ, Kramer JC. Perron P. et al: A compar ison of several hypertonic solutions for resuscita tion of bled sheep. J Surg Res 1985;39:517-528. Baue AE, Tragus ET, Parkins WM: A comparison of isotonic and hypertonic solution blood on blood flow and oxygen consumption in the initial treatment of hemorrhage shock. J Trauma 1967;7: 743-756. Nakayama S, Sibley L, Gunther R: Small volume resuscitation with hypertonic saline (2,400 mosm/ liter) during hemorrhagic shock. Circ Shock 1989; 13:149-159. Koch-Weser J: Influence of osmolarity of perfu sate on contractility of mammalian myocardium. Am J Physiol 1963;204:957-962. Kreimeier U, Brueckner U B. Messmer K: Improve ment of nutritional blood flow using hypertonic solution for primary treatment of hemorrhagic hy potension. Eur Surg Res 1988;20:277-279. Loveday E: Resuscitation of conscious pigs fol lowing hemorrhage: Renal function before and after 7.5% NaCl/6% dextran solution administra tion. Circ Shock 1988:24:248. Prough DS, Johnson JC, Poole GV, et al: Effects of intracranial pressure of resuscitation from hem orrhagic shock with hypertonic saline versus lactated Ringer’s solution. Crit Care Med 1987;43: 407-411. Poole GV Jr, Johnson JC, Prough DS, et al: Cere bral hemodynamics after hemorrhagic shock: Ef fects of the type of resuscitation fluid. Crit Care Med 1986;14:629-633. Crook JN, Gray LW Jr, Nance FC, Cohn I Jr: Upper gastrointestinal bleeding. Ann Surg 1972; 175:771-782. Received: June 25, 1990 Accepted: January 2, 1991 Adolfo Chávez-Negrete, MD Hospital de Especialidades Centro Médico La Raza IMSS Depto. Medicina Interna Seris y Zaachila, Col. La Raza CP 2990 Azcapotzalco México DF (Mexico)
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more, a greater amount of blood was trans fused in patients of the control group. This findings might reflect the beneficial influence of the rapid improvement of blood pressure and tissue perfusion due to H/H solutions. Nevertheless, the outcome could also be ascribed to a different severity of bleeding during follow-up. 250 ml of H/H solution, either by the peripheral vein or the intraosseous route, showed to be useful in reversing short-time hypotension due to severe upper gastrointes tinal bleeding.
129
© 199! S. Karger AG, Basel 0014-312X/91/O232-0123S2.75/0
Treatment of Hemorrhagic Shock with Intraosseous or Intravenous Infusion of Hypertonic Saline Dextran Solution A. Chavez-Negretea , S. M ajluf Cruz*, A. Frati Munari*. A. Perchesb , R. Argueroc “Department of Internal Medicine, bDepartment of Gastroenterology, d ep a rtm en t of Heart Surgery, La Raza Medical Center, IMSS, Mexico City, Mexico
Key Words. Hemorrhage • Hypertonic saline • Hypotension • Hypovolemia • Shock • Intraosseous infusion • Hyperoncotic solution
Gastrointestinal hemorrhage is one of the commonest causes of emergency room ad mission in the world [1], Mortality due to this cause ranges from 9 to 29% in North America [2] and it is up to 65% if the bleed ing is due to esophageal varices [3], In these cases, quick large intravenous fluid infusions
are required and the infusion of equally ef fective rapidly infused low-volume solution should be advantageous. Hypertonic hyper oncotic solution (7.5% NaCl/dextran 70) has been found effective in resuscitating animals from hemorrhagic shock, even in volumes as low as 4 ml/kg [4, 5]. Holcroft et al. [6, 7]
Downloaded by: Univ.of California Berkeley 128.32.10.230 - 7/26/2018 10:20:31 AM
Abstract. The efficacy of intravenous or intraosseous infusion of 250 ml of 7.5% NaCl and 6% dextran 60(H/H) was compared with intravenous Ringer’s lactate (RL) for the initial treatment of patients with hemorrhagic shock due to upper gastrointestinal bleeding. 49 patients were randomly assigned to receive either H/H (n = 26) or RL (n = 23). In the first 16 patients with H/H and in all RL patients, solutions were infused by the intravenous route, while the intraosseous route through sternal puncture was chosen for the last 10 H/H sub jects. H/H patients were analyzed together since no differences were noticed between the routes of infusion. The H/H group also received 2.3 ± 0.7 liters of intravenous cristalloid solutions in the first hour and 4.4 ± 0.1 liters in the 24-hour period, while RL received 3.3 ± 0.7 and 7.3 ± 2.4 liters, respectively. Blood pressure (BP) increased during the first 15 min in the H/H group (from 61 ± 17/30 ± 12 to 85 ± 30/48 ± 14 mm Hg) and thereafter, while remaining unchanged in the RL group (from 75 ± 18/40 ± 12 to 75 ± 17/40 ± 14 mm Hg; p < 0.05). The differences between groups were significant throughout 24 h. Urine output and improvement of the Glasgow Coma Score were also higher in H/H patients than in the control group (p < 0.05). There were 5 deaths in RL group and 1 in the H/H group. Sternal of peripheral vein infusion of 250 ml of 7.5% NaCl/6% dextran 60 is an effective initial treat ment of hemorrhagic shock.
124
Châvez-Negrete/Majluf Cruz/Frati Munari/Perches/Argüero
Table 1. Clinical data on entry H/H (7.5% NaCl/6% dextran 60) — i.v (n = 16)
i.o (n = 10)
Age, years Mean Range
42 22-76
41
44
42 52-58
Gender (M/F)
18/8
10/6
8/2
14/9
Blood pressure Systolic, mm Hg Diastolic, mm Hg
64 ±21 32± 14
56 ±18 17± 10
63 ±20 33 ±17
75 ± 18 40 ±12
Heart rate
113 ± 15
119 ± 16
109 ±13
112 ± 19
Hb. g/dl
8.6 ±2
8.2 ± 2
9.4±2
8.6 ± 3
Hct, %
29 ± 6
29 ±7
30 ±5
27 ± 8
9±2
9±2
9± 1
!0 ± 1
9 7 -
3 4 3
9 14 -
Glasgow Coma Score Etiology of bleeding Peptic ulcer Esophageal varices Others
12 11 3
reported improved blood pressure and sur vival with hypertonic saline/dextran solu tion in severely injured patients. Also in pa tients with hemorrhagic shock, wide intrave nous catheters are needed. However, the in sertion of wide catheters is not always easy in patients with hypovolemia and collapsed pe ripheral veins [8]. This problem can be solved using alternative routes to infuse fluids. Intraosseous infusion has been pro posed as an alternative route to reach the blood stream since it provides a rapid vascu lar access [9], This is a prospective, controlled study which evaluates the administration of hypertonic/hyperoncotic (H/H) solutions through the intravenous or intraosseous route in the management of hemorrhagic shock due to gastrointestinal bleeding.
Patients and Methods Adult patients with acute gastrointestinal hemor rhage and arterial hypotension were selected from the Emergency Room of Gastroenterology and Internal Medicine Departments. Inclusion criteria were: (a) systolic blood pressure equal or lower than 90 mm Hg for less than 1 h; (b) normal electrocardiogram, and (c) written consent by the patients or if it was not possible by a first-degree relative. Patients were not included when pregnancy, renal, cardiac or neurolog ical diseases were present. 49 consecutive patients were assigned by random numbers to be treated either with 250ml of 7.5% NaCl/6% dextran 60 solution (H/H) (Schiwa GmbH, Glandorf, FRG) (group 1) or conventional lactated Ringer’s (LR) (group 2). H/H has an osmolality of 2,400 mosm/1 while LR has 276 mosm/1. All solutions were administered as soon as possible (on admission or few minutes after the begin ning of bleeding if patients were already hospitalized) by peripheral vein in the first 16 patients of group 1 and in all patients of group 2, while the intraosseous route was used in the last 10 patients with H/H. When
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total (n = 26)
LR i.v. (lactated Ringer's) (n - 23)
Hypertonie Saline Dextran in Hemorrhagic Shock
the intraosseous route was chosen, a 1.5-cm deep ster nal puncture was performed with a 14-gauge needle which was inserted between the second and third intercostal space [9]. At the end of H/H or Ringer lactate infusion, sup plemental isotonic saline fluid was administered through the peripheral vein in both groups as neces sary in order to achieve a systolic blood pressure higher than 100 mm Hg. In addition, dextran 40 was administered to the control group if necessary accord ing to medical judgement. Packed red cells were transfused if bleeding or hypotension was present after the first 15 min of treatment, or if they reap peared within the next 24 h. Also, standard etiological treatment was carried out in every case (e.g. patients with esophageal varices required a Sengstaken-Blakemore tube, those with peptic ulcer received antacid and cimetidine). Blood pressure, heart rate, Glasgow Coma Score at 15, 30 and 60 min and 4, 8 and 24 h were recorded. Blood count, BUN, serum creatinine, and serum electrolytes and arterial gases were deter mined at arrival and at 24 h. All data in figures and tables are presented as mean ± SD. Statistical methods were analysis of vari ance and paired Student’s t test, p < 0.05 was consid ered significant. The study was approved by the Hos pital Ethical-Investigation Committee.
125
Fig. 1. Blood pressure after H/H infusion of up to 24 h by peripheral vein (n = 16; •), intraosseous route (n « 10; o) and LR group (n = 23; o). A significant difference was noticed (p < 0.05) between the H/H group and control group at 15 min after infusion. No differences were found between intraosseous or intra venous infusion in the H/H group. For clarity pur poses, only mean values are shown.
Fourty-nine patients were studied: 26 re ceived H/H through the peripheral vein (16 patients) or by the intraosseous route (10 patients) while 23 individuals were in the control group with LR. There were no differ ences in initial demographic or clinical data, or blood pressure, pulse rate or therapeutic response between patients who received H/H solution by the peripheral vein or by the intraosseous route. Thus they were further analysed as a whole group. On entry, age, gender, blood pressure, heart rate, Glasgow Coma Score, hematocrit as well as the etiol ogy and site of hemorrhage were similar in group 1 and 2 (table 1). A nearly identical
significant increase in BP was noted 15 min after sternal or intravenous infusion of H/H (63 ± 21/33 ± 17/91 ± 20/50 ± 20 and 61 ± 17/30 ± 12 to 85 ± 30/48 ± 14 mm Hg, respectively). Blood pressure rose from 15 min on and thereafter with the infusion of H/H with sta tistical significance (p < 0.05) as compared with the control group (fig. 1). Hypotension persisted for at least 1 h in several patients of the control group despite rapid infusion of intravenous fluids. Patients of group 1 re ceived 2,360 ± 723 ml of cristalloid solu tions in the first hour, while subjects of group 2 received 3,312 ± 750 ml in the same
Downloaded by: Univ.of California Berkeley 128.32.10.230 - 7/26/2018 10:20:31 AM
Results
Chavcz-Negrete/Vlajluf Cruz/Frati Munari/Perches/Argiiero
Fig. 2. Heart rate values after H/H (intraosseous and peripheral vein; n - 26; •) vs. LR group (n = 23; o). Bars indicate the SD. Differences between groups were not significant (p > 0.05).
period. Heart rate decreased throughout the 24 h in both groups, without difference be tween groups (fig. 2). 24-Hour urine output was higher in group 1 than in group 2 although group 1 re ceived only 4,400 ± 188 ml of supplemental fluids in 24 h while in group 2 7,300 ± 2,400 ml were infused in the same period (fig. 3). Serum electrolytes at the time of en try and after 24 h were within normal limits in both groups (data not shown). The amount of packed red cells transfused was also higher in controls (950 ± 500 ml) than in the H/H group (480 ± 200 ml p < 0.05). Most patients of group 2 received two or more units of packed red cells while only 7 subjects of group 1 received two or three units (table 2). In spite of transfusions, only
Fig. 3. 24-Hour urine output af ter H/H (intraosseous and periph eral vein) infusion vs. LR group (p < 0.05) and supplemental fluids in both groups (p = NS).
Downloaded by: Univ.of California Berkeley 128.32.10.230 - 7/26/2018 10:20:31 AM
126
127
Hypertonie Saline Dextran in Hemorrhagic Shock
a mild nonsignificant improvement of ane mia was noticed at 24 h in both groups which reflects the magnitude of the hemor rhage. On entry, pa02 was lower in the H/H group than in the control group; however, it rose close to normal limits in the following 24 h (table 3). A significant improvement of neurological status was also noticed in H/H patients reaching statistical significance at 24 h (p < 0.05) (fig. 4). The improvement was best noticed in those patients with an initial Glasgow Coma Score lower than 10 (table 4). Within the 24 h of the study, 5 patients died in the control group while only 1 died in the H/H group.
Table 2. Packed red cell requirement Solutions
7.5% NaCl/6% dextran 60 Lactatcd Ringer’s
Units (300 ml) 0
1
2
4 0
15 1
6 13
3 >4 1 3
0 6
Fig. 4. Glasgow Coma Score at entry and after 24 h in patients receiving H/H (7.5% NaCl/6% dextran 60) or LR (lactatcd Ringer’s). Though improve ment was seen in both groups, it was significant only in the H/H group (p < 0.05, Mann-Whitney U test). The differences between the number of patients who improved in H/H vs. LR were also significant (p < 0.02, Fisher’s test).
Table 3. Arterial blood gases Entry
1h
24 h
pH
H/H LR
9 6
7.37 + 0.3 7.36±0.4
7.4 ±0.8 7.34±0.7
7.42 ±0.6 7.36±0.2
pCOi, mm Hg
H/H LR
9 6
17.8 ±1.04 34.1+2
20.8 ±4 34.6 ± 1
23.27 ±2.2* 35.2 ±1.4
pO;, mm Hg
H/H LR
9 6
44.5 ± 15 61.5 + 5
HCOt, mEq/1
H/H LR
9 6
11.9 ± 2 18.6 ± 7
Results expressed as X ± SD. * p < 0.05: entry vs. 24 h later. No mechanical ventilation was used (FI0., 21 %).
65± 16 69 ± 18 14.4 ±2 22 ±2
67± 17* 62 ±4 17.2 ±4* 22 ±8 Downloaded by: Univ.of California Berkeley 128.32.10.230 - 7/26/2018 10:20:31 AM
n
128
Table 4. Glasgow Coma Score Solution
n
Entry Score after score 24 h X ± SD
7.5% NaCl/6% dextran 60
10 6
< 10 + 5.5+ 1.4* > 10 + 2.16 ± 0.4
Lactatcd Ringer’s
0 ± 0 .5 b 10 < 10 6 > 10 +1.9 ± 1.5
* p < 0.05 a versus b.
Discussion Velasco et al. [10] reported in 1980 that 4 ml/kg of 7.5% NaCl solution was effective in resuscitating animals from hypovolemic shock. Later, Smith et al. [11] found that the combination of 7.5% sodium chloride with 6% dextran 70 was more effective than hy pertonic saline alone; this solution also re stored acid-base balance, urine output and tissue oxygen consumption in hypovolemic animals [12], Holcroft et al. [6, 7] showed that a similar hypertonic/hyperoncotic solu tion (7.5% saline/4.2% dextran 70) en hanced blood pressure in severely injured patients. In this study, H/H solution was effective in patients with severe hemorrhage restoring blood pressure within few minutes, and the beneficial effect lasted for the next 24 h. Re markably, in the control group, blood pres sure did not immediately rise in spite of large volume replacement. The immediate hemodynamic effects of H/H solution can be ascribed to its hyperosmolality, which causes plasma volume expansion [13], enhance ment of myocardial contractility [14] and higher blood pressure, leading to a rise of
organ blood flow [12, 15]. In this study, blood pressure increased as well as urine out put. The last may be the result from both higher renal blood flow [16] and osmotic diuresis. The improvement in arterial pCL after H/H may be a consequence of better hemodynamic conditions. Neurological improvement measured by the Glasgow Coma Score that was noticed mostly in patients treated with H/H solution was consistent with the overall clinical sta tus. Although we did not measure intracra nial pressure, it is noteworthy that in experi mental animals, resuscitation from hemor rhagic shock with isotonic fluids resulted in enhancement of intracranial pressure while hypertonic fluids maintain low intracranial pressure [17, 18], Intraosseous injection of H/H has been proposed as a rapid means of gaining vascu lar access when peripheral cannulation is dif ficult [9], Intraosseous infusion is easy to per form and does not require special training. In the present study, 10 patients were injected into the sternum with 250 ml of H/H without complications. Volume expansion with this method was as rapid and effective as periph eral vein infusion. This method may be use ful in emergencies if peripheral veins are not readily accessible. In this study, no complica tions ascribed to H/H solution or to intraos seous sternal infusion were seen. It is known that conventional therapy and emergency surgery have failed to reduce the overall mortality of bleeding from esophageal varices [19], Likewise, in this study, mortal ity was due to hemorrhage from esophageal varices in all the cases. In the H/H group there was only 1 death, while there were 5 deaths in the control group, although both groups were similar in initial clinical status, hematocrit and cause of bleeding. Further
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Chávez-Negrete/Majluf Cruz/Frati Munari/Perches/Argüero
Hypertonie Saline Dextran in Hemorrhagic Shock
References 1 Gostout CJ: Acute gastrointestinal bleeding - A common problem revisisted. Mayo Clin Proc 1988;63:596-604. 2 Halmagyi AF: A critical review of 425 patients with upper gastrointestinal hemorrhage. Surg Gy necol Obstet 1970;130:419-430. 3 Westaby D, Macongall B, Williams R: Improved survival following injection sclerotherapy for esophageal varices. Final analysis of a controlled trial. Hepatology 1985;5:827-830. 4 Kramer GC, Perron PR. Lindsey DC. et al: Smallvolume resuscitation with hypertonic saline dextran solution. Surgery 1986;100:239-246. 5 Maningas PA, De Guzman LR, Tillman FJ, et al: Small volume infusion of 7.5% NaCI in dextran 70 for the treatment of severe hemorrhagic shock in swine. Ann Emcrg Med 1986; 15:1131-1137. 6 Holcroft JW, Vassar MJ, Tunncr JE, et al: 3% NaCI and 7.5% NaCl/dextran 70 in the resuscita tion o f severely injured patients. Ann Surg 1987; 206:279-286. 7 Holcroft JW, Vassar MJ, Perry CA, et al: Perspec tives on clinical trials for hypertonic saline/dextran solutions for the treatment of traumatic shock. Brazilian J Med Biol Res I989;22:291293. 8 Smith Jp, Bosai BI, Hill AS, Frey CF: Prehospital stabilization of critically injured patients: A failed concept. J Trauma 1985;25:65-70. 9 Saavedra J, Patterson HA, Kramer GC: Intraos
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seous injection of hypertonic saline dextran. Ana tomic considerations in man and sheep. Circ Shock 1988;24:283. Velasco LT, Pontieri V, Rocha-e Silva M Jr. Lopez OU: Hyperosmotic NaCI and severe hemorrhagic shock. Am J Physiol 1980;239:H664-H673. Smith GJ, Kramer JC. Perron P. et al: A compar ison of several hypertonic solutions for resuscita tion of bled sheep. J Surg Res 1985;39:517-528. Baue AE, Tragus ET, Parkins WM: A comparison of isotonic and hypertonic solution blood on blood flow and oxygen consumption in the initial treatment of hemorrhage shock. J Trauma 1967;7: 743-756. Nakayama S, Sibley L, Gunther R: Small volume resuscitation with hypertonic saline (2,400 mosm/ liter) during hemorrhagic shock. Circ Shock 1989; 13:149-159. Koch-Weser J: Influence of osmolarity of perfu sate on contractility of mammalian myocardium. Am J Physiol 1963;204:957-962. Kreimeier U, Brueckner U B. Messmer K: Improve ment of nutritional blood flow using hypertonic solution for primary treatment of hemorrhagic hy potension. Eur Surg Res 1988;20:277-279. Loveday E: Resuscitation of conscious pigs fol lowing hemorrhage: Renal function before and after 7.5% NaCl/6% dextran solution administra tion. Circ Shock 1988:24:248. Prough DS, Johnson JC, Poole GV, et al: Effects of intracranial pressure of resuscitation from hem orrhagic shock with hypertonic saline versus lactated Ringer’s solution. Crit Care Med 1987;43: 407-411. Poole GV Jr, Johnson JC, Prough DS, et al: Cere bral hemodynamics after hemorrhagic shock: Ef fects of the type of resuscitation fluid. Crit Care Med 1986;14:629-633. Crook JN, Gray LW Jr, Nance FC, Cohn I Jr: Upper gastrointestinal bleeding. Ann Surg 1972; 175:771-782. Received: June 25, 1990 Accepted: January 2, 1991 Adolfo Chávez-Negrete, MD Hospital de Especialidades Centro Médico La Raza IMSS Depto. Medicina Interna Seris y Zaachila, Col. La Raza CP 2990 Azcapotzalco México DF (Mexico)
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more, a greater amount of blood was trans fused in patients of the control group. This findings might reflect the beneficial influence of the rapid improvement of blood pressure and tissue perfusion due to H/H solutions. Nevertheless, the outcome could also be ascribed to a different severity of bleeding during follow-up. 250 ml of H/H solution, either by the peripheral vein or the intraosseous route, showed to be useful in reversing short-time hypotension due to severe upper gastrointes tinal bleeding.
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