Storage of an avulsed permanent tooth prior to reimplantation, Revised); (FA 794) Systematic Review

Conflict of Interest Declaration

The ILCOR Continuous Evidence Evaluation process is guided by a rigorous ILCOR Conflict of Interest policy. There were no declared conflicts of interest

CoSTR Citation

Borra V, De Brier N, O D, Berry D, Hood N, Djärv T, Zideman D, Singletary E on behalf of the International Liaison Committee on Resuscitation First Aid Task Force.

Storage of an avulsed tooth prior to replantation Consensus on Science with Treatment Recommendations [Internet] Brussels, Belgium: International Liaison Committee on Resuscitation (ILCOR) First Aid Task Force, 2019 December 12. Available from http://ilcor.org

Methodological Preamble and Link to Published Systematic Review

The continuous evidence evaluation process for the production of the Consensus on Science with Treatment Recommendations (CoSTR) started with a systematic review of storage techniques for an avulsed permanent tooth prior to replantation conducted by the Centre for Evidence-Based Practice (CEBaP) at the Belgian Red Cross, Mechelen, Belgium with involvement of clinical content experts from the ILCOR First Aid Task Force.

The critical outcome of viability was measured in most studies as cell viability by harvesting periodontal ligament (PDL) cells, staining them with 0.4% (w/v) trypan blue and counting them under a light microscope with a hemocytometer.

NOTE FOR RISK OF BIAS:

In most cases bias was assessed per comparison rather than per outcome, since there were no meaningful differences in bias across outcomes. In cases where differences in risk of bias existed between outcomes this was noted.

Systematic Review

Webmaster to insert the Systematic Review citation and link to PubMed using this format when it is available.

PICOST

The PICOST (Population, Intervention, Comparator, Outcome, Study Designs and Timeframe)

Population: Adults and children in any setting (in-hospital or out-of-hospital) with an avulsed permanent tooth

Intervention: Any storage media, container or technique.

Comparators: Storage in whole milk or the patient’s saliva.

Outcomes: Success of replantation and tooth survival or viability (critical outcomes). Color of the tooth, infection rate, malfunction (eating, speech) and pain (important outcomes).

Study Designs: Randomized controlled trials (RCTs) and non-randomized studies (non-randomized controlled trials, interrupted time series, controlled before-and-after studies, cohort studies) are eligible for inclusion.

Timeframe: All years and all languages were included as long as there was an English abstract; unpublished studies (e.g., conference abstracts, trial protocols) were excluded. Literature search updated to September 2, 2019.

PROSPERO Registration: CRD42020152903

Consensus on Science

Hank’s Balanced Salt Solution (HBSS) (I) compared with milk (C)

For the critical outcome of viability (number of viable periodontal ligament cells (PDL)) we have identified low-certainty evidence (downgraded for risk of bias and indirectness) from 12 randomized studies {Abraham 2019 ZC11}{Ahangari 2013 244}{Chen 2012 158}{Doyle 1998 221}{Gopikrishna 2008 e61}{Khademi 2008 25}{Martin 2004 85}{Prueksakorn 2016 495}{Rajendran 2011 217}{Subramaniam 2015 62}{Sunil 2013 JC005C}{Talebi 2018 203} and one observational study{Bag 2017 458} including 422 extracted teeth, showing benefit from 15 min to 24 h immersion in HBSS when compared with low fat milk, whole milk, or skim milk (SMD, 2.47; 95%, 1.59-3.34; P<0.00001).

No benefit for the critical outcome of viability (number of viable PDL cells) was found in one randomized study{Nabavizadeh 2018 28} and two observational studies{Caglar 2010 383}{Caglar 2015 21}, including 32 extracted teeth. These studies reported only median cell viability and thus absolute effects could not be calculated. One other observational study{Pileggi 2002 186} also failed to show benefit from use of HBSS when compared with milk (unspecified) or 2.5 % fat milk but did not report the number of extracted teeth (P>0.05).

Propolis (I) compared with milk (C)

For the critical outcome of viability (number of viable PDL cells) we have identified very-low-certainty evidence (downgraded for risk of bias, indirectness and imprecision) from 3 randomized studies{Ahangari 2013 244}{Martin 2004 85}{Prueksakorn 2016 495} including 86 extracted teeth, showing benefit for 45 to 180 min immersion in propolis, when compared with milk (unspecified) (SMD, 1.73; 95% CI, 1.12–2.33; P<0.00001).

Oral Rehydration Salts (ORS) (I) compared with milk (C)

For the critical outcome of viability (number of viable PDL cells) we have identified very-low-certainty evidence (downgraded for risk of bias, indirectness and imprecision) from 2 randomized studies{Rajendran 2011 217}{Subramaniam 2015 62} including 100 extracted teeth, showing benefit from 45 to 90 min immersion in ORS when compared with milk (unspecified) or whole milk (SMD, 4.16; 95% CI, 2.10–6.23; P<0.0001).

Ricetral (I) compared with milk (C)

For the critical outcome of viability (number of viable PDL cells), we identified very-low-certainty evidence (downgraded for risk of bias, indirectness, and imprecision) from 1 randomized study{Gopikrishna 2008 e61} including 20 extracted teeth, showing benefit from 45 min of immersion in ricetral when compared with milk (unspecified) (MD, 44.3; 95% CI, 12.82–75.78; P=0.006).

Coconut water (I) compared with milk (I)

For the critical outcome of viability (number or percentage of viable PDL cells), we have identified very-low-certainty evidence (downgraded for risk of bias, inconsistency between trials, indirectness and imprecision) from 4 randomized studies{D’Costa 2017 107}{Gopikrishna 2008 e61}{Kokkali 2017 209}{Sunil 2013 JC005C} including 96 extracted teeth, showing benefit in 3 studies from 45 min immersion in coconut water (MD, 23%; 95% CI, 19.57-26.43; P<0.00001; MD, 339.4; 95% CI, 331.65-347.15; P<0.00001; MD, 260.12; 95% CI, 236.43-283.81; P<0.00001) and showing harm in the Kokkali study from 45 min immersion in coconut water (MD, -9293.33; 95% CI, -10930.14 – -7656.52; P<0.00001) when compared with milk (unspecified).

Egg white (I) compared with milk (C)

For the critical outcome of viability (number or percentage of viable PDL cells), we have identified very-low-certainty evidence (downgraded for risk of bias, indirectness and imprecision) from 4 randomized studies{Ahangari 2013 244}{Khademi 2008 25}{Sharma 2015 524}{Sharma 2016 408} including 50 extracted teeth, not showing benefit from 30 min to 12 h immersion in egg white when compared with milk (unspecified) (SMD, 0.14; 95% CI, -0.52–0.80; P=0.60).

Rice water (I) compared with milk (C)

For the critical outcome of viability (number or percentage of viable PDL cells) we have identified very-low-certainty evidence (downgraded for risk of bias, indirectness and imprecision) from 1 randomized study{Sharma 2016 408} including 30 extracted teeth, showing benefit from 30 min immersion in rice water when compared to milk (unspecified) (MD, 11; 95% CI, 5.29–16.71; P<0.00001).

Cling film (I) compared with milk (C)

For the critical outcome of viability (as measured by the probability and rate of PDL cell growth), we have identified very-low-certainty evidence (downgraded for risk of bias, indirectness and imprecision) from 1 randomized study{Zeissler-Lajtman 2017 954} including 14 extracted teeth, showing benefit in rate of cell growth after 7 and 14 days following 120 min storage in cling film when compared with immersion in milk (unspecified) (MD, 0.45; 95% CI could not be calculated and MD, 0.41; 95% CI could not be calculated; P=0.033; respectively).

Tap water (I) compared with milk (C)

For the critical outcome of cell viability (percentage of viable PDL cells), we have identified very-low-certainty evidence (downgraded for risk of bias, indirectness and imprecision) from 1 randomized study{Talebi 2018 203} including 120 extracted teeth, showing harm from 60 min, 180 min, 6 h and 24 h immersion in tap water when compared with skim milk (MD, -18.53%; 95% CI, -23.53– -13.53; MD, -16.47; 95% CI, -22.56– -10.38; MD, -15.2%; 95% CI, -18.52– -18.22; MD, -7.33%; 95% CI, -9.26– -5.40; P<0.00001, respectively).

One observational study{Pileggi 2002 186} did not report the number of extracted teeth in the groups but showed harm from 45 min immersion in tap water when compared with milk (unspecified) (MD, -45.42; 95% CI could not be calculated; P<0.05).

Buttermilk (I) compared with milk (C)

For the critical outcome of viability (number of viable PDL cells), we have identified very-low-certainty evidence (downgraded for risk of bias, indirectness and imprecision) from 1 randomized study{Kokkali 2017 209} including 30 extracted teeth showing harm from 45 min immersion in buttermilk when compared with milk (unspecified) (MD, -12646; 95% CI, -14084.66– -11208.48; P<0.00001).

Castor oil (I) compared with milk (C)

For the critical outcome of viability (percentage of viable PDL cells), we have identified very-low-certainty evidence (downgraded for risk of bias, indirectness and imprecision) from 1 randomized study{Nabavizadeh 2018 28} including 20 extracted teeth showing harm from 45 min immersion in castor oil when compared with 2.5 % fat milk (only median cell viability reported, thus absolute effects could not be calculated; P<0.05).

Turmeric extract (I) compared with milk (C)

For the critical outcome of viability (percentage of viable PDL cells), we have identified very-low-certainty evidence (downgraded for risk of bias, indirectness and imprecision) from 1 randomized study{Dhimole 2019 140} including 60 extracted teeth showing harm from 30 min immersion in turmeric extract when compared with milk (unspecified) (MD, -8.35%; 95% CI, -11.29– -5.41; P<0.00001).

Neem extract (I) compared with milk (C)

For the critical outcome of viability (percentage of viable PDL cells), we identified very-low-certainty evidence (downgraded for risk of bias and imprecision) from 1 randomized study{Dhimole 2019 140} with 60 avulsed teeth not showing benefit from 30 min immersion in Neem extract when compared with milk (unspecified) (MD, -1.98; 95% CI, -4.54–0.58, P=0.13).

0.9 % Saline solution (I) compared with milk (C)

For the critical outcome of viability (percentage of viable PDL cells), we have identified very-low-certainty evidence (downgraded for risk of bias, inconsistency, indirectness and imprecision) from 3 randomized studies and 2 observational studies{D’Costa 2017 107}{Hegde 2016 45}{Martin 2004 85}{Patil 1994 1}{Sunil 2013 JC005C} including 104 extracted teeth, showing harm from 30 to 120 min immersion in 0.9 % saline solution when compared with milk (unspecified) (SMD, -4.35; 95% CI, -7.55– -1.14; P=0.008).

Two observational studies {Caglar 2010 383}{Caglar 2015 21} including 12 extracted teeth reported only median cell viability and thus absolute effects could not be calculated. One non-randomized study (Pileggi 2002 186) did not report the number of extracted teeth in the groups. These studies do not show benefit from immersion in 0.9 % saline solution when compared with milk (unspecified) (P>0.05).

For the critical outcome of success of replantation (as measured by PDL cell healing or functional healing) we have identified very-low-certainty evidence (downgraded for risk of bias and imprecision) from 3 observational studies{Pohl 2005 93}{Wang 2019 251}{Werder 2011 312} with 102 avulsed teeth not showing benefit from immersion in 0.9 % saline solution when compared with milk (unspecified) (RR, 1.20; 95% CI, 0.74–1.95; P=0.47; 75 teeth more per 1000; 95% CI, from 98 fewer to 356 more).

0.9 % Saline solution (I) compared with saliva (C)

For the critical outcome of success of replantation (as measured by pulpal healing, PDL healing or functional healing), we have identified very-low-certainty evidence (downgraded for risk of bias and imprecision) from 2 observational studies{Andreasen 1995 59}{Andreasen 1995 76} with 90 avulsed teeth, not showing benefit for immersion in 0.9% saline solution when compared with saliva (RR, 0.97; 95% CI, 0.53–1.79; P=0.92; 8 teeth fewer per 1000; 95% CI, from 119 fewer to 201 more).

Probiotic media (I) compared with milk (C)

For the critical outcome of viability (number of viable PDL cells), we have identified very-low-certainty evidence (downgraded for risk of bias, indirectness, and imprecision) from 2 observational studies{Caglar 2010 383}{Caglar 2015 21} each with 12 extracted teeth, reporting only median cell viability and thus absolute effects could not be calculated (median difference 116 000 and 95 0000, respectively). These studies fail to show benefit from immersion in probiotic media when compared with milk (unspecified) (P>0.05).

Aloe vera gel (I) compared with milk (C)

For the critical outcome of viability (number of viable PDL cells), we have identified very-low-certainty evidence (downgraded for risk of bias and imprecision) from 2 randomized studies{Abraham 2019 ZC11}{Sharma 2015 408} including 50 avulsed teeth, showing benefit in one study from immersion in aloe vera gel when compared with milk (unspecified) (MD, 14.20; 95% CI, 8.72–19.68; P<0.00001) and showing harm in the second study from immersion in aloe vera gel when compared with low fat milk (MD, -571.7; 95% CI, -875.1– -268.3).

Saliva (I) compared with milk (C)

For the critical outcome of success of replantation (measured by PDL cell healing), we have identified very-low-certainty evidence (downgraded for risk of bias and imprecision) from 3 observational studies{Chappuis 2005 289}{Karayilmaz 2013 464}{Wang 2019 251} including 70 avulsed teeth not showing benefit from immersion in saliva when compared with milk (unspecified) (RR, 0.96; 95% CI, 0.65–1.43; P=0.86; 19 teeth fewer per 1000; 95% CI, from 167 fewer to 206 more).

Eagle’s Medium (aMEM) (I) compared with saliva and thereafter milk (C)

For the critical outcome of viability (as measured by clonogenic capacity of PDL cells (%)), we have identified very-low-certainty evidence (downgraded for risk of bias, indirectness, and imprecision) from 1 observational study{Lekic 1998 137} with 10 extracted teeth showing a trend towards improved viability from 30 and 60 min immersion in aMEM when compared with saliva and thereafter milk (unspecified) (MD, 5% higher and 12.5% higher, respectively, 95% CI and P-value were not estimable).

Epigallocatechin-3-Gallate (EGCG) (I) compared with milk (C)

For the critical outcome of viability (percentage of viable PDL cells), we identified very-low-certainty evidence (downgraded for risk of bias, indirectness, and imprecision) from 1 randomized study{Chen 2012 158} with 20 extracted teeth, not showing benefit from 2 hours of immersion in EGCG when compared with whole milk (MD, 9.8 %; 95% CI, −8.66–28.26, P=0.31).

Storage in another person’s mouth (I) compared with storage in the patient’s mouth (C)

For the critical outcome of success of replantation (as measured by pulpal healing), we identified very-low-certainty evidence (downgraded for risk of bias and imprecision) from 2 observational studies{Andreasen 1995 59}{Andreasen 1995 76} with 28 avulsed teeth, not showing benefit for pulpal healing after storage in another person’s mouth when compared with storage in the patient’s mouth (RR, 1.0; 95% CI, 0.31–3.18, P=1.00; 0 teeth fewer per 1000; 95% CI, from 197 fewer to 623 more).

Dentosafe® box (I) compared with milk (C)

For the critical outcome of success of replantation (as measured by periodontal or functional healing), we identified very-low-certainty evidence (downgraded for risk of bias and imprecision) from 3 observational studies{Chappuis 2005 289}{Pohl 2005 93}{Werder 2011 312} with 71 avulsed teeth not showing benefit from storage in a Dentosafe® box when compared with milk (unspecified) (RR, 1.20; 95% CI, 0.61-2.36, P=0.59; 108 teeth more per 1000; 95% CI, from 210 fewer to 732 more)..

Dentosafe® box (I) compared with saliva (C)

For the critical outcome of success of replantation (as measured by periodontal healing), we identified very-low-certainty evidence (downgraded for risk of bias and imprecision) from 1 observational study{Chappuis 2005 289} with 21 avulsed teeth not showing benefit from storage in a Dentosafe® box when compared with saliva (RR, 0.83; 95% CI, 0.35–1.98, P=0.68; 102 teeth fewer per 1000; 95% CI, from 390 fewer to 588 more).

GC Tooth Mousse (I) compared with milk (C)

For the critical outcome of viability (percentage viable PDL cells), we identified very-low-certainty evidence (downgraded for risk of bias and imprecision) from 1 observational study{Hedge 2016 45} with 57 avulsed teeth showing harm from 30 min immersion in GC Tooth Mousse (MD, -2 %; 95% CI, -3.39– -0.61, P=0.005) and after 60 min immersion in GC Tooth Mousse (MD, -2.3 %; 95% CI, -3.91– -0.69, P=0.005) when compared with milk (unspecified).

Saliva and thereafter HBSS (I) compared with saliva and thereafter milk (C)

For the critical outcome viability (measured as clonogenic capacity (%)), we identified very-low-certainty evidence (downgraded for risk of bias and imprecision) from 1 observational study{Lekic 1998 137} with 10 avulsed teeth, not showing benefit from 30 min immersion in saliva and thereafter HBSS (MD, -1; 95% CI could not be calculated, P>0.05) but showing benefit from 60 min immersion in saliva and thereafter HBSS when compared with saliva and thereafter milk (unspecified) (MD, 2.4; 95% CI could not be calculated; P<0.05).

Table 1: overview of all comparisons, the certainty of evidence and the evidence conclusion. The beneficial interventions that are recommended in the treatment recommendation are highlighted in green.

Treatment Recommendations

We suggest the use of Hank’s Balanced Salt solution (HBSS), propolis (from 0.04 mg to 2.5 mg per ml 0.4% ethanol), Oral Rehydration Salt solutions including ricetral [Oral Rehydration Salt solutions containing sodium chloride, glucose, potassium chloride, citrate (or extruded rice)], or cling film compared with any form of cow’s milk for temporary storage of an avulsed tooth that cannot be immediately replanted (weak recommendation, very low certainty evidence).

If none of the above choices are available, we suggest the use of cow’s milk, any percent fat or form, compared with tap water, buttermilk, castor oil, turmeric extract or saline (sodium chloride) for temporary storage of an avulsed tooth (weak recommendation, very low certainty evidence).

There is insufficient evidence to recommend for or against temporary storage of an avulsed tooth in saliva compared with alternative solutions.

There is insufficient evidence to recommend for or against temporary storage of an avulsed tooth in probiotic media, Epigallocatechin-3-Gallate, Dentosafe® box, or egg white compared with cow’s milk.

Justification and Evidence to Decision Framework Highlights

• We identified many studies evaluating different storage solutions or techniques for avulsed teeth. Table 1 is an overview of all different comparisons, including the number and certainty of studies for each comparison and the direction of the results. This table is meant to provide a summarized overview of all the different comparisons.
• In making these recommendations, we recognize that survival of an avulsed tooth requires that it must be replanted as soon as possible, but this procedure may not be possible in the first aid setting. The use of a suitable temporary storage solution or technique for an avulsed tooth should not delay efforts at replantation, but it may aid in the survival of the tooth before replantation.
• The original wording of this PICO question specified use of whole milk as a comparison. After the initial search results were reviewed, it was recognized that the studies identified use cow’s milk as the comparator, but with varying percentages of fat content, and some milk was pasteurized or homogenized. We therefore only recommend that cow’s milk be used, without a specific fat percentage. Fat content of milk, pasteurization, homogenization and temperature were not evaluated and are therefore a limitation of this review.
• This updated treatment recommendation varies from the previous treatment recommendations in 2015{Singletary 2015 S269}{Zideman 2015, e229} in that:
  • We no longer recommend coconut water as a storage solution as recent studies provide conflicting evidence; nor do we recommend egg white, since the beneficial effect was not confirmed by new studies.
• ORS, rice water and cling film are added as recommended solutions or techniques for temporary storage of an avulsed tooth when compared with milk.
• The recommendation to store an avulsed tooth in milk in comparison with saline is retained, but we now also recommend storage in milk before tap water, buttermilk, castor oil and turmeric extract.
• Cling film is easily applicable since it is available in almost all households and widely available. It has a very limited cost.
• Oral Rehydration Solution (ORS) is available in most first aid kits, and therefore easily applicable in all settings.
• Although evidence from 1 study shows benefit for immersion in rice water when compared with milk, the task force decided not to recommend it. If rice water must be made (i.e., boiling rice in water and allowing to cool) this could create a delay and it may therefore be preferable to use an alternative storage technique that is readily available.

A recommendation was not made for Eagle’s Medium (aMEM), aloe vera or coconut water because of inconclusive or conflicting evidence.

Knowledge Gaps

• There is a lack of observational studies with traumatic avulsed teeth (instead of extracted teeth), measuring tooth viability (not cell viability), and success of replantation.
• In a future PICO question, replanting the tooth in the dental socket versus storage in a temporary storage medium could be compared.

Is training in dental replantation for first aid providers feasible and effective?

Attachment

EtD

FA794-Et D-Dental-avulsion-tap-water-butter-milk-castor-oil-turmeric-extract-vs-milk

FA794-Et D-Dental-avulsion-rice-water-vs-milk

FA794-Et D-Dental-avulsion-ORS-vs-milk

FA794-Et D-Dental-avulsion-Cling-film-vs-milk

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