Secondary Logo

Journal Logo

Blood Products, Crystalloids, and Rapid Infusion

An Experimental Study

Gopinath, Anupama MBChB, MRes; Nelson, Chaim MD; Gupta, Anupriya MD; Bonney, Iwona PhD; Schumann, Roman MD

doi: 10.1213/ANE.0000000000001183
Cardiovascular Anesthesiology: Research Report

BACKGROUND: Electromagnetic coil overheating, deformation, occlusion, and rupture during rapid infuser use have been previously reported. Although the etiology is unclear, prolonged machine use and reconstitution of citrated blood components with crystalloid solutions in the reservoir have been implicated. Lactated Ringer’s (LR) solution is of particular concern as a diluent because of its calcium content. We sought to reproduce this failure mode using different infusion rates and different combinations of fluids for blood product reconstitution in the reservoir. We also introduced calcium chloride (CaCl2) to the mix to determine its role in macroscopic clot formation.

METHODS: In this in vitro study, we conducted 2 series of experiments using the Belmont FMS 2000 rapid infuser and a reservoir. In series I, we submitted a mix of 1 U fresh thawed plasma (FTP) and 1 U red blood cells (RBC) with 500 mL of LR solution, normal saline, Plasma-Lyte A, or albumin 5% to a specific pump flow sequence. If neither a pump failure mode or self-shutoff (primary outcome) nor macroscopic clot (secondary outcome) was observed during a pump flow sequence, the sequences were repeated after first adding an additional 500 mL of the initially used crystalloid or albumin and then CaCl2 beginning with 200 mg and up to 1 g to the reservoir. In series II, 7 different crystalloid-blood product combinations were tested by using a variety of pump flow sequences with the same end points. Descriptive statistics and analysis of variance were used, and data were reported as means ± SD.

RESULTS: We did not observe a Belmont pump failure mode (coil deformation, occlusion, or rupture) as previously described. In series I, the addition of CaCl2 200 mg resulted in macroscopic clots in 9 of 10 experiments (95% confidence interval, 0.55–0.99). The time to clot formation was 9.1 ± 2.3 minutes (99% confidence interval, 6.74–11.46) and did not differ between solutions used for component reconstitution. In series II, adding variable amounts of CaCl2 to 4 different combinations of FTP/RBC with Plasma-Lyte A or LR solution led to clot formation. The use of only FTP in 2 experiments with either LR solution or normal saline resulted in formation of a fibrin clot. In 1 experiment of LR solution mixed with RBCs alone, no clot was observed even after addition of 1 g CaCl2. After the observation of clot in the reservoir, the fluid empty alarm occurred once in series I, the overheating alarm occurred once in series II, and the high-pressure alarms occurred 3 times in each series, all accompanied by self-shutoff.

CONCLUSIONS: In this in vitro study, we were unable to reproduce the failure mode characterized by coil overheating, deformation, and rupture previously reported with use of the FMS 2000. Addition of CaCl2 in the range of 200 mg caused macroscopic coagulation in the reservoir when added to crystalloids or albumin mixed with different combinations of blood products containing FTP.

From the Department of Anesthesiology, Tufts Medical Center, Boston, Massachusetts.

Accepted for publication December 18, 2015.

Funding: Department of Anesthesiology, Tufts Medical Center. Disposables for the study were provided by the Belmont Instrument Corporation, Billerica, MA. Blood products were provided by the Blood Bank of Tufts Medical Center.

The authors declare no conflicts of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website.

Drs. Gopinath and Nelson have contributed equally to this work and should be considered co-first authors.

Reprints will not be available from the authors.

Address correspondence to Roman Schumann, MD, Department of Anesthesiology, Tufts Medical Center, 800 Washington St., Box# 298, Boston, MA 02111. Address e-mail to

A variety of rapid volume infusers are available to assist in the resuscitation of trauma patients or in cases with the potential for sudden, life-threatening hemorrhage. Massive transfusion often relies on the use of such infusers, which are designed to safely deliver warmed fluids and blood products across a wide range of flow rates. These devices use different mechanisms for pumping and warming fluid, including pressure chambers or roller pumps, and countercurrent heating systems or electromagnetic induction heating coils. The Belmont FMS 2000 rapid infuser (Belmont Instrument Corporation, Billerica, MA) uses a roller pump and heating coil arrangement and offers the use of a reservoir for high-volume infusion. Because these infusion devices have a pumping function, blood products need not be diluted with crystalloid to facilitate flow. However, in clinical practice, the reservoir and pump may be loaded and primed with a combination of crystalloid and blood products.

After a case report of coil overheating and deformation by Husser et al.,1 a more recent case series by Xia et al.2 described the use of the Belmont FMS 2000 system during liver transplantation where overheating to >42°C and blood clot occlusion of the electromagnetic heating coil with subsequent inability to administer fluids were observed. The authors hypothesized that blood clot formation led to heating coil occlusion, stasis, and subsequent overheating. Among 12 overheated units used by Xia et al.,2 calcium was found in the 2 that were sent off-site for analysis. However, the authors reported no use of calcium or calcium-containing solutions and, in a separate account, described 23 additional cases of overheating.3 In 1 instance, calcium was detected exclusively downstream from the heating coil and none in the reservoir or upstream.3 The role of calcium in pump failure events is thus unclear.

We hypothesized that 1 potential mechanism for coil occlusion, overheating, and damage may be the interaction of calcium-containing crystalloids with reconstituted citrated blood products in the reservoir. We further hypothesized that variability in pump speeds during prolonged periods of use could also contribute to or trigger pump occlusion.

Therefore, the purposes of this study were as follows:

  1. To reproduce the Belmont FMS 2000 pump failure mode previously reported using different combinations of crystalloids and blood products in the reservoir and applying escalating pump flow rates in a closed-loop model.
  2. To evaluate the effect of different crystalloid types, albumin, and calcium chloride (CaCl2) addition on the incidence of macroscopic clot formation and pump failure.
Back to Top | Article Outline


Blood Products and Fluids

We used fresh thawed plasma (FTP) and red blood cells (RBC) that either recently expired or had experienced a storage violation prohibiting further clinical use. These blood products were donated to the study by the institutional blood bank, and donated FTP and RBC were kept at 4°C until start of the study. Both FTP and RBC were derived from donated whole-blood units anticoagulated with calcium-phosphate-dextrose. RBC anticoagulation also included calcium-phosphate-dextrose adenine-1 for cell preservation.

The specific crystalloids tested (Baxter Healthcare Corporation, Deerfield, IL) were lactated Ringer’s (LR) solution, 0.9% normal saline (NS) solution, and Plasma-Lyte A (PL) solution. In addition, we also tested 5% human albumin solution (Alb; Grifols Biologicals Inc., Los Angeles, CA). All crystalloids and albumin used were stored at room temperature until use.

Back to Top | Article Outline

Study Protocol

We conducted an IRB-approved, observational in vitro study using the Belmont FMS 2000 with a reservoir. During the experiments, a closed circuit was created by connecting the pump output line to the reservoir input inside the filtration chamber (Fig. 1). We conducted 2 separate series of experiments, series I and series II. Except for 1 experiment in series II where 4 units of blood product were used, all other experiments were performed with a maximum of only 2 units of blood product because of the limited and sporadic supply of compatible components.

Figure 1

Figure 1

In series I, a combination of 1 unit FTP and 1 unit RBC with 500 mL of 1 of 3 different crystalloid solutions or albumin were mixed into the reservoir and then cycled through the infusion device and back into the reservoir (Fig. 1). This closed-loop system allowed the mix in the reservoir to be constantly agitated as it would be in clinical practice during high-volume replacement, yet it provided for a constant, controlled crystalloid/blood component composition during each pump flow sequence. Each mixture was then submitted to a flow sequence (A–D) and a stepwise addition of CaCl2 to the reservoir as shown in Figure 2. The experiment was performed twice for each fluid and blood product combination. LR solution was tested for an additional 2 times for a total of 10 series I experiments.

Figure 2

Figure 2

We hypothesized that the addition of calcium to blood products containing clotting factors such as FTP may contribute to inadvertent coagulation. Because 1 L LR solution contains approximately 200 mg CaCl2, in series I (Fig. 2), we added CaCl2 at an initial dose of 200 mg to the reservoir if no pump failure or coagulation occurred after sequences A and B.

In series II, we conducted 7 additional experiments with different fluid and blood component combinations based on product availability (Table 1). In each experiment, a specific combination of diluent (crystalloid or albumin), packed RBC, and FTP was subjected either to the flow sequence as in Figure 2 or a different flow sequence and the addition of variable amounts of CaCl2 (Supplemental Digital Content,

Table 1

Table 1

All experiments ended when either an end point was reached or a maximal amount of 1 g CaCl2 was added.

A dedicated observer checked the pump for the previously described failure mode or any pump alarm and self-shutoff (primary outcome) and the reservoir for the development of macroscopic clot (secondary outcome). We defined pump failure as coil occlusion, deformation, and rupture or any instance during which the pump would stop operating because of its safety mechanisms and alarm, including overheating and high line pressure. When a clot was observed in the reservoir without first triggering a pump stop, the pump flow and machine behavior were assessed for up to an additional 5 minutes of operation. The flow rate, stage of the experiment at the time of reaching a study end point, and any subsequent pump stop and alarm message were recorded. The heating coil of the pump insert was visually inspected and digitally photographed.

We used Stata/IC 13.1 (StataCorp, College Station, TX) for the 1-way analysis of variance method to compare the time to clot observation among the different fluid and blood product combinations, and the Clopper-Pearson test to determine the 95% confidence interval (CI) for the point estimate of clot observation in series I. We assumed a non-normal distribution to calculate the 99% CI for the time to clot formation in series I. Because of the lack of homogeneity with respect to variables that might influence the presence of an alarm in each of the 2 series, 99% CIs were calculated for these point estimates to be more conservative.

A P value <0.05 was considered statistically significant. Data were reported as means ± SD.

Back to Top | Article Outline


A failure mode characterized by overheating, deformation, and rupture of the electromagnetic heating coil in the Belmont FMS 2000 rapid infuser could not be reproduced in our study.

In series I, no clot was observed in any experiment in sequences A and B. The addition of 200 mg CaCl2 to 1 L of PL solution, NS, LR solution, or albumin in sequence C produced the secondary study end point of macroscopic clot in the reservoir in 9 of the 10 experiments (95% CI, 0.55–0.99) (Figs. 2 and 3). The mean time to clot formation after the most recent addition of CaCl2 in series I experiments was 9.1 ± 2.3 minutes (99% CI, 6.74–11.46). The time to clot formation did not differ with fluid type (P = 0.56).

Figure 3

Figure 3

Of the 7 experiments in series II, we performed 5 experiments with LR solution, 1 experiment with NS, and 1 with PL solution by using different blood product combinations (Table 1; Supplemental Digital Content, We observed no evidence of coagulation in the single experiment of LR solution mixed with RBC alone, even when we added an additional 1 g CaCl2. However, when we mixed LR solution or NS with FTP only and added 200 mg CaCl2, we detected a fibrin clot that subsequently passed into the patient delivery line beyond the heating coil (Fig. 4). In both instances, either the high-pressure or the overheating alarm triggered. In 1 series II experiment after adding calcium to PL solution, RBC, and FTP, a clot was also found in the patient delivery line.

Figure 4

Figure 4

Pump alarms and self-shutoff were noted only after a clot was observed in the reservoir when the infuser was allowed to keep running as follows: the pump safety stop engaged in 3 of 10 in series I and 3 of 7 in series II experiments because of a high-pressure alarm (99% CI, 0.037–0.735 and 99% CI, 0.055–0.882, respectively). The fluid empty alarm and the overheating alarm occurred once in series I and II, respectively (99% CI, 0.0005–0.544 and 99% CI, 0.007–0.684, respectively; Table 2). We did not observe any differences in appearance or clotting between the left and the right side of the heating coil as previously reported.2 Instead, we noted irregular, island-shaped markings on the metallic surface inside the heating coil at the end of the experiments that differed little between each test (Fig.5).

Table 2

Table 2

Figure 5

Figure 5

We did not observe clot formation when combining LR solution, FTP, and RBC in any series I or II study without adding CaCl2.

The postexpiration ages in days for RBC and FTP were 8.5 ± 13.3 and 13.9 ± 14.2 (mean ± SD) in series I and 14.3 ± 19.7 and 7.4 ± 5.8 in series II.

Back to Top | Article Outline


Rapid infusion devices are commonly used in clinical practice, and device failure can adversely affect patient care. Assuming that a properly functioning device is appropriately handled by the clinician, the true incidence of device failure is unknown. The Food and Drug Administration provides the Manufacturer and User Facility Device Experience database that contains mandated and voluntary device reports including from manufacturers, device user facilities, health care professionals, and consumers.a We performed a simple search with the terms Belmont Instrument Corporation, FMS 2000, and Belmont rapid infuser. Examination of the results revealed 44 distinct reports between 2004 and the last update of the database at the time of this writing, August 2015. The reports involved 18 instances of the overheating alarm, 4 instances of heating element deformation, and 2 high-pressure alarms during this 11-year period. Information regarding reservoir use or content was insufficient to gain any insights into patterns of causation, and the number of unreported events remains uncertain. According to the manufacturer, almost 4000 Belmont FMS 2000 rapid infuser devices have been purchased worldwide and 60,000 of its disposables have been sold in 2014 (data supplied by Belmont Instrument Corporation).

In clinical practice, RBCs and other blood components may be reconstituted with crystalloids to improve flow and to prime rapid infuser reservoirs. Although studies have examined the coagulation potential of crystalloids with RBCs and FTP separately, there is very little information about crystalloid with RBC/FTP combinations regarding potential clot formation. In this in vitro study, combining FTP and RBCs with different types of crystalloid or albumin in the Belmont FMS 2000 rapid infuser with a reservoir, we were unable to re-create the warming unit overheating with coil deformation and rupture event reported by others.1,2 However, 1 overheating, 1 fluid empty, and several high-pressure alarms were triggered when we allowed continuing pump operation for 5 minutes after the observation of a macroscopic clot in the reservoir (a study end point).

Despite the dilution of 1 unit each of FTP and RBC with 1 L of NS, PL solution, LR solution, and albumin 5%, respectively, we consistently observed macroscopic clot formation in the reservoir after the addition of 200 mg CaCl2. Spontaneous clotting did not occur during our trial. Xia et al.2 also observed immediate clot formation in the reservoir and safety stop of the pump when they added 300 mg CaCl2 to 500 mL LR solution mixed with 2 units each of RBCs and FTP in 1 experiment.

Series II experiments demonstrated clot formation when 200 mg CaCl2 was added to 1 L LR solution or NS mixed with 2 U FTP. No coagulation occurred in the experiment where 1 L LR solution was combined with 2 U RBCs despite the addition of up to CaCl2 1 g. The latter observation suggests that only a very small amount of clotting factors remain in currently available RBC units. Our results indicate that in the presence of coagulation factors (i.e., FTP), ≤200 mg CaCl2 may trigger macroscopic clot formation even when blood products are diluted to a 0.7:1 ratio.

The deliberate addition of CaCl2 to a blood component mix in a reservoir is unlikely to occur in clinical practice. It is conceivable that calcium may be added downstream from the reservoir into the patient line. However, this clinical use is unlikely to trigger a clot because the combination is rapidly flushed into the bloodstream.

At no time did coagulation occur immediately or with CaCl2 addition, but with a delay during the pump flow sequence. In our series I experiments, the time to coagulation when the fluid mixture was warmed and agitated by transit through the closed-loop system was 9.1 ± 2.3 minutes, suggesting that CaCl2-induced coagulation is a time-dependent process. With a clotting time of 9 minutes, it is possible that low pump flow rates used in clinical practice may provide adequate time for clotting to occur. Although the postexpiration age of the blood components had a range from 0 to 48 days, we found no effect of the type of fluid on the time to coagulation. After clot appearance in the reservoir, the high-pressure alarm was observed in 3 series I and 3 series II experiments, and the fluid empty alarm and the overheating alarm occurred once in series I and II, respectively. Although we allowed continued rapid infuser operation for up to 5 minutes after clot observation (secondary end point), it is conceivable that allowing the pump to continue running beyond this limited time of observation might have produced additional alarms and self-shutoff events.

Crystalloids and compatibility with blood pertaining to clot formation have been investigated in several in vitro studies with different designs, and current guidelines recommend not mixing LR solution with blood products during IV infusion because of its CaCl2 content. Two studies described clotting with the mixing of LR solution and whole blood.4,5 In one of these studies, clotting with LR solution and whole blood became visible after a 5-minute incubation period at room temperature.

LR solution and RBC combination clotting potential has been investigated separately. In 1 in vitro study, LR solution was mixed with RBCs in a 1:1 volume ratio (200 mL total), and macroscopic red cell aggregation was found with LR solution containing CaCl2 5 g/L but not 2 g/L.6 Cull et al.7 examined different RBC/LR solution dilutions and noted clotting at dilutions of 1:1 but not 5:1, 3:1, and 2:1. They concluded that reconstitution of RBC with LR solution was safe when RBC were present in greater volume than with LR solution.7 A more recent in vitro study did not find any macroscopic or microscopic clot when NS or LR solution was added to RBC over a range of dilution ratios from 10:1 to 1:2 (crystalloid to RBC).8 In our experiment of mixing LR solution with RBC only, the crystalloid to RBC ratio was closer to 1:0.7, and we did not observe macroscopic coagulation or coil occlusion even with the addition of 1 g calcium.

When choosing crystalloids to combine with coagulation factor containing blood components, clinicians should also be mindful of the risk of hyperchloremic metabolic acidosis associated with administration of large amounts of NS.9

The systematic investigation of blood component and fluid combinations in rapid infusion devices in a simulated clinical practice setting is hampered by ethical limitations in the use of blood products eligible for use in humans. In our study, 1 important limitation is that we used blood products beyond their recommended storage date. The postexpiration ages of RBC and FTP were highly variable, which may have affected some of our results. With increasing age of RBC, structural changes take place, including increased osmotic fragility, hemolysis, and loss of deformability that may decrease effective clot formation.10,11 Aucar and Sheth12 demonstrated in vitro that RBC cold storage beyond 3 weeks after donation results in decreased coagulation with FTP.

The use of FTP after 5 days of cold storage at 1 to 6°C is not recommended for clinical use, and clotting factor activity decline may have affected our results. However, the decline of hemostatic factor activity in FTP is gradual and most significant for factors V and VIII within the first 24 hours after thawing.13 Furthermore, it has been demonstrated that coagulation factor activity in refrigerated FTP at 4°C for 2 weeks and up to 28 days was still sufficient for adequate hemostasis.14,15 Some of the differences in our findings may also be explained by the variable volume of each unit of blood product. Although RBC and FTP contain typically between 300 to 350 mL and 275 to 350 mL per unit, respectively, the amount in each experiment is never exactly the same, reflecting clinical practice. We also did not investigate microscopic clot formation because this would not be available during clinical care. In future trials, continuing pump operation beyond our observation in the presence of macroscopic clot formation may further clarify the effects of clot on pump operation.

In conclusion, we were unable to replicate the coil occlusion, overheating, and damage previously reported with use of the Belmont FMS 2000 by combining LR solution, NS, PL solution, or albumin with FTP and RBC and additional CaCl2. Our results suggest a role for calcium as an initiator of coagulation in blood products containing hemostatic factors. Although we used 200 mg CaCl2, there is the possibility that less CaCl2 may suffice to induce clotting in our model.

Although current accepted guidelines recommend avoiding LR solution for reconstitution of citrated blood components containing clotting factors and coadministration of calcium-containing medications,16 our results indicate that reconstituting blood products with LR solution may be possible in some circumstances. Additional studies are needed to explore this possibility.

Back to Top | Article Outline


Name: Anupama Gopinath, MBChB, MRes.

Contribution: This author helped conduct the study, collect the data, analyze the data, and prepare the manuscript.

Attestation: Anupama Gopinath approved the final manuscript and attests to the integrity of the original data and the analysis reported in this manuscript.

Name: Chaim Nelson, MD.

Contribution: This author helped design the study, conduct the study, collect the data, and prepare the manuscript.

Attestation: Chaim Nelson approved the final manuscript and attests to the integrity of the original data and the analysis reported in this manuscript.

Name: Anupriya Gupta, MD.

Contribution: This author helped conduct the study, collect the data, and data entry.

Attestation: Anupriya Gupta approved the final manuscript and attests to the integrity of the original data and the analysis reported in this manuscript.

Name: Iwona Bonney, PhD.

Contribution: This author helped collect the data and prepare the manuscript.

Attestation: Iwona Bonney approved the final manuscript.

Name: Roman Schumann, MD.

Contribution: This author helped design the study, conduct the study, collect the data, analyze the data, and prepare the manuscript.

Attestation: Roman Schumann approved the final manuscript and attests to the integrity of the original data and the analysis reported in this manuscript and is the archival author.

This manuscript was handled by: Avery Tung, MD.

Back to Top | Article Outline


a MAUDE—Manufacturer and User Facility Device Experience. Available at: Accessed July 31, 2015.
Cited Here...

Back to Top | Article Outline


1. Husser CS, Chamblee B, Brown MJ, Long TR, Wass CT. Inductive warming of intravenous fluids: overheating of the toroid heating element during rapid infusion. Anesthesiology. 2004;101:1019–21
2. Xia VW, Huh M, Ross N, Nourmand H, Wang C, Steadman RH. Overheating and rupture of FMS 2000 rapid infuser. J Cardiothorac Vasc Anesth. 2011;25:1092–4
3. Xia VW, Huh M, Ross N, Nourmand H, Wang C, Steadman RH. Reply to Dr. Herzlinger. J Cardiothorac Vasc Anesth. 2011;25:e56–57
4. Ryden SE, Oberman HA. Compatibility of common intravenous solutions with CPD blood. Transfusion. 1975;15:250–5
5. Dickson DN, Gregory MA. Compatibility of blood with solutions containing calcium. S Afr Med J. 1980;57:785–7
6. Lorenzo M, Davis JW, Negin S, Kaups K, Parks S, Brubaker D, Tyroch A. Can Ringer’s lactate be used safely with blood transfusions? Am J Surg. 1998;175:308–10
7. Cull DL, Lally KP, Murphy KD. Compatibility of packed erythrocytes and Ringer’s lactate solution. Surg Gynecol Obstet. 1991;173:9–12
8. Albert K, van Vlymen J, James P, Parlow J. Ringer’s lactate is compatible with the rapid infusion of AS-3 preserved packed red blood cells. Can J Anaesth. 2009;56:352–6
9. Lira A, Pinsky MR. Choices in fluid type and volume during resuscitation: impact on patient outcomes. Ann Intensive Care. 2014;4:38
10. Chin-Yee I, Arya N, d’Almeida MS. The red cell storage lesion and its implication for transfusion. Transfus Sci. 1997;18:447–58
11. Card RT, Mohandas N, Perkins HA, Shohet SB. Deformability of stored red blood cells. Relationship to degree of packing. Transfusion. 1982;22:96–101
12. Aucar JA, Sheth M. The storage lesion of packed red blood cells affects coagulation. Surgery. 2012;152:697–702
13. Sheffield WP, Bhakta V, Mastronardi C, Ramirez-Arcos S, Howe D, Jenkins C. Changes in coagulation factor activity and content of di(2-ethylhexyl)phthalate in frozen plasma units during refrigerated storage for up to five days after thawing. Transfusion. 2012;52:493–502
14. Smak Gregoor PJ, Harvey MS, Briët E, Brand A. Coagulation parameters of CPD fresh-frozen plasma and CPD cryoprecipitate-poor plasma after storage at 4 degrees C for 28 days. Transfusion. 1993;33:735–8
15. Lamboo M, Poland DC, Eikenboom JC, Harvey MS, Groot E, Brand A, de Vries RR. Coagulation parameters of thawed fresh-frozen plasma during storage at different temperatures. Transfus Med. 2007;17:182–6
16. Maynard KFung MK. Administration of blood and components. In: Technical Manual. 2014;54518th ed Bethesda, MD American Association of Blood Banks:534–60

Supplemental Digital Content

Back to Top | Article Outline
© 2016 International Anesthesia Research Society